Performance of Tests for Schistosoma Haematobium Diagnosis

Stefanie Knopp801 enrolled

Overview

Urogenital schistosomiasis caused by infection with the blood fluke Schistosoma haematobium is a debilitating disease. The World Health Organization (WHO) has set the goal to eliminate schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Many years of control interventions and mass drug administration have reduced substantially the prevalence and infection intensities in several areas. In areas with an infection prevalence \<10%, the WHO suggests to continue population preventive chemotherapy with praziquantel at the same or reduced frequency, or to use a clinical approach of test-and-treat. In areas that have achieved interruption of transmission, elimination needs to be validated and post-elimination surveillance be implemented. For determination of infection prevalence thresholds, for test-and-treat, for validation of elimination and for pre- and post-elimination surveillance, reliable diagnostic tools are needed. In a single-centre study conducted in Pemba, United Republic of Tanzania, the investigators aim to assess the accuracy and performance of standard and new diagnostic tests for S. haematobium diagnosis for use in elimination settings. The primary objective of the study is to assess the sensitivity and specificity of all investigated diagnostic tests, using the S. haematobium egg count results of five urine filtrations conducted on five urine samples collected over five consecutive days as reference test. Secondary objectives are: * To assess the sensitivity and specificity of all investigated diagnostic tests, using latent class analyses. * To assess the sensitivity and specificity of all investigated diagnostic tests, in relation to S. haematobium infection intensity, calculated as mean egg count derived from the egg counts in five urine samples collected over 5 consecutive days. * To assess the sensitivity and specificity of all investigated diagnostic tests, in relation to S. haematobium infection intensity, calculated from the egg counts of the urine sample that was analysed with the respective test and urine filtration. * To assess the sensitivity and specificity of all investigated diagnostic tests, using the results of the up-converting reporter particle-lateral flow circulating anodic antigen assay (UCP-LF CAA) as reference test. * To assess the sensitivity and specificity of all investigated molecular diagnostic tests, using the results of the qPCR as reference test. * To assess the cost and time needed for the implementation of single or multiple-throughput tests. Our study will evaluate the accuracy and performance of diagnostic tests, in a formerly highly endemic setting that is now approaching elimination (Pemba), and will hence provide important information about which tests can be recommended for threshold determination, and test-and-treat and surveillance.

Interventions

S. haematobium egg detection by single urine filtrationDIAGNOSTIC_TEST

The urine samples of children participating in the initial screening will be tested with a single urine filtration by human microscopy.

S. haematobium egg detection by quintuple urine filtrationDIAGNOSTIC_TEST

Five urine samples will be collected from children participating in the diagnostic study over five days. Each of the five urine samples collected per participant will be tested with a single urine filtration by human microscopy.

S. haematobium egg detection by artificial intelligence (AI) microscopyDIAGNOSTIC_TEST

The urine samples collected on Day 5 of the diagnostic study will be tested with artificial intelligence (AI) microscopy.

Haematuria assessment using reagent stripsDIAGNOSTIC_TEST

The urine samples collected from children participating in the initial screening and in the diagnostic study, respectively, will be tested with reagent strips.

S. haematobium antigen detection by up-converting reporter particle-lateral flow circulating anodic antigen assay (UCP-LF CAA)DIAGNOSTIC_TEST

The urine samples collected on Day 5 of the diagnostic study will be tested with the up-converting reporter particle-lateral flow circulating anodic antigen assay (UCP-LF CAA).

S. haematobium DNA detection by recombinase polymerase amplification assay (RPA)DIAGNOSTIC_TEST

The urine samples collected on Day 5 of the diagnostic study will be tested with the recombinase polymerase amplification assay (RPA).

S. haematobium DNA detection by qPCRDIAGNOSTIC_TEST

The urine samples collected on Day 5 of the diagnostic study will be tested with qPCR

Eligibility

Sex: ALLMin age: 6 YearsMax age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Subjects fulfilling all of the following inclusion criteria are eligible for the initial screening: * Attendance of grade 3, 4, 5, or 6 in study school * Randomized to participate in initial screening * Written informed consent signed by the parents * Written assent signed by the participant if aged12-17 years old Subjects fulfilling all of the following inclusion criteria are eligible for the diagnostic study: * Attendance of grade 3, 4, 5, or 6 in study school * Randomized to participate in initial screening * Written informed consent signed by the parents * Written assent signed by the participant if aged12-17 years old * S. haematobium-positive urine filtration result in initial screening OR * S. haematobium-negative urine filtration result in initial screening, but randomized for participation in diagnostic study Exclusion Criteria: The presence of any one of the following exclusion criteria will lead to the exclusion of the subject in the initial screening: * Not attending any study school * Not attending grade 3, 4, 5 or 6 * Not randomized to participate in initial screening * No written informed consent signed by the parents submitted * No written assent signed by the participant if aged12-17 years old submitted * S. haematobium-negative urine filtration result in initial screening, and not randomized for participation in diagnostic performance study * Clinical significant sever disease The presence of any one of the following exclusion criteria will lead to the exclusion of the subject in the diagnostic study: * Not attending any study school * Not attending grade 3, 4, 5 or 6 * Not randomized to participate in initial screening * No written informed consent signed by the parents submitted * No written assent signed by the participant if aged12-17 years old submitted * S. haematobium-negative urine filtration result in initial screening, and not randomized for participation in diagnostic performance study * Clinical significant sever disease

Outcomes

Primary Outcomes

Accuracy of tests for S. haematobium diagnosis when compared with a single urine filtration

The primary endpoint will be the sensitivity of the investigated diagnostic tests to detect S. haematobium related markers by the examination of a single sample. The primary outcome variable will be the number of S. haematobium infected individuals detected through each test.

Time frame: From enrollment to the end of the study after 6 weeks

Secondary Outcomes

Sensitivity of each diagnostic test (human microscopy, AI microscopy, reagent strips, RPA, UCP-CAA, qPCR).

Sensitivity is defined as the proportion of positive test results out of all truly positive samples. Reference tests are human microscopy, UCP-CAA, qPCR or a combination thereof, performed with the same urine sample (human microscopy, UCP-CAA, qPCR) or quintuple urine samples (human microscopy).