Trial Design for a Diagnostic Accuracy Study of a Point-of-Care Test for the Detection of Taenia solium Taeniosis and (Neuro)Cysticercosis in Community Settings of Highly Endemic, Resource-Poor Areas in Zambia: Challenges and Rationale

Abstract

Field-applicable, high-quality, and low-cost diagnostic tools are urgently needed for Taenia solium. The aim of this paper is to describe the design, challenges, and rationale for the design of a diagnostic accuracy study in low-resource community settings in Zambia. The trial was designed as a prospective study with a two-stage design to evaluate a new point-of-care test (TS POC) for the detection of taeniosis and (neuro)cysticercosis. Participants within randomly selected households were tested with the TS POC test (index test). Participants who tested TS POC positive for taeniosis and/or cysticercosis and a subset of the negatives were requested to give blood and stool samples for reference testing, and to undergo clinical examination and a cerebral CT scan. The difficulties of conducting a clinical trial in settings with limited research and neuroimaging infrastructure as well as peculiarities specifically related to the disease (low prevalence of taeniosis and the lack of a gold standard) were taken into consideration for the design of this study. The two-stage design increased the efficiency of the study by reducing the number of samples, clinical examinations, and CT scans. Simplified flows and sampling processes were preferred over complex follow-up and randomization systems, aiming to reduce bias and increase the generalizability of the study.

Trial Design of a Prospective Multicenter Diagnostic Accuracy Study of a Point-of-Care Test for the Detection of Taenia solium Taeniosis and Neurocysticercosis in Hospital-Based Settings in Tanzania

“…A detailed description of the TS POC test is presented in [ 11 ]. To summarize, the TS POC test is an antibody-detecting prototype developed by a team of researchers from the USA and Germany.…”

“…Sample collection, processing, shipment, and analysis were the same as for the SOLID project community-based study in Zambia [ 11 ]. To summarize, 3 mL of venous blood was collected, and the serum was stored at −20 °C until reference testing using the LLGP-EITB, recombinant immunoblots (rES33 and rT24H), and Ag ELISA.…”

“…A procedure as described for the community-based study in Zambia was followed [ 11 ]. For group 1, all patients were seen by a doctor ( Figure 2 ) who performed a neurological examination, while for groups 2 and 3 ( Figure 3 ) only study participants TS POC CC-positive were seen by a study doctor.…”

“…Patients who underwent a CT scan were informed about the results during a follow-up appointment, and management procedures as described for the community-based study in Zambia were followed [ 11 ]. In short, if indicated, anthelmintic treatment was offered according to national guidelines and Winkler et al If indicated, anthelmintic treatment with albendazole (15 mg/kg/d) was offered for 10 days, accompanied with corticosteroid treatment (dexamethasone 12 mg to 20 mg/d), starting one day before and ending three days after anthelmintic treatment with half the dosage.…”

“…The main objective of the SOLID project (“Evaluation of an antibody-detecting point-of-care test for the diagnosis of Taenia solium taeniosis and neurocysticercosis in communities and primary care settings of highly endemic, resource-poor areas in Tanzania and Zambia, including the training of—and technology transfer to the Regional Reference Laboratory and health centers”) was to evaluate the sensitivity/specificity and ease of use of the TS POC test for the detection of T. solium T and NCC in resource-poor, highly endemic areas in sub-Saharan Africa. The study in Zambia was conducted in a community-based setting and its design was published elsewhere [ 11 ]. This paper focuses on the design of the diagnostic accuracy evaluation of the TS POC test at the district hospital level in Tanzania.…”