Validation of artificial intelligence-based digital microscopy for automated detection of Schistosoma haematobium eggs in urine in Gabon.

INTRODUCTION: Schistosomiasis is a significant public health concern, especially in Sub-Saharan Africa. Conventional microscopy is the standard diagnostic method in resource-limited settings, but with limitations, such as the need for expert microscopists. An automated digital microscope with artificial intelligence (Schistoscope), offers a potential solution. This field study aimed to validate the diagnostic performance of the Schistoscope for detecting and quantifying Schistosoma haematobium eggs in urine compared to conventional microscopy and to a composite reference standard (CRS) consisting of real-time PCR and the up-converting particle (UCP) lateral flow (LF) test for the detection of schistosome circulating anodic antigen (CAA). METHODS: Based on a non-inferiority concept, the Schistoscope was evaluated in two parts: study A, consisting of 339 freshly collected urine samples and study B, consisting of 798 fresh urine samples that were also banked as slides for analysis with the Schistoscope. In both studies, the Schistoscope, conventional microscopy, real-time PCR and UCP-LF CAA were performed and samples with all the diagnostic test results were included in the analysis. All diagnostic procedures were performed in a laboratory located in a rural area of Gabon, endemic for S. haematobium. RESULTS: In study A and B, the Schistoscope demonstrated a sensitivity of 83.1% and 96.3% compared to conventional microscopy, and 62.9% and 78.0% compared to the CRS. The sensitivity of conventional microscopy in study A and B compared to the CRS was 61.9% and 75.2%, respectively, comparable to the Schistoscope. The specificity of the Schistoscope in study A (78.8%) was significantly lower than that of conventional microscopy (96.4%) based on the CRS but comparable in study B (90.9% and 98.0%, respectively). CONCLUSION: Overall, the performance of the Schistoscope was non-inferior to conventional microscopy with a comparable sensitivity, although the specificity varied. The Schistoscope shows promising diagnostic accuracy, particularly for samples with moderate to higher infection intensities as well as for banked sample slides, highlighting the potential for retrospective analysis in resource-limited settings. TRIAL REGISTRATION: NCT04505046 ClinicalTrials.gov.

Performance evaluation of the AiDx multi-diagnostic automated microscope for the detection of schistosomiasis in Abuja, Nigeria.

In this research, we report on the performance of automated optical digital detection and quantification of Schistosoma haematobium provided by AiDx NTDx multi-diagnostic Assist microscope. Our study was community-based, and a convenient sampling method was used in 17 communities in Abuja Nigeria, based on the disease prevalence information extracted from the baseline database on schistosomiasis, NTD Division, of the Federal Ministry of Health. At baseline, samples from 869 participants were evaluated of which 358 (34.1%) tested S. haematobium positive by the reference diagnostic standard. Registered images from the fully automated (autofocusing, scanning, image registration and processing, AI image analysis and automatic parasite count) AiDx assist microscope were analyzed. The Semi automated (autofocusing, scanning, image registration & processing and manual parasite count) and the fully automated AiDx Assist showed comparable sensitivities and specificities of [90.3%, 98%] and [89%, 99%] respectively. Overall, estimated egg counts of the semi-automated & fully automated AiDx Assist correlated significantly with the egg counts of conventional microscopy (r = 0.93, p ≤ 0.001 and r = 0.89, p ≤ 0.001 respectively). The AiDx Assist device performance is consistent with requirement of the World Health Organization diagnostic target product profile for monitoring, evaluation, and surveillance of Schistosomiasis elimination Programs.

Image-Based Awareness Campaign and Community Mobilization in the Control of Schistosomiasis.

Community awareness and participation in mass screening is critical for schistosomiasis control. This study assessed the impact of sharing anonymized image-based positive test results on the uptake of screening during community mobilization outreach. We conducted an observational study to compare the population response to standard and image-based strategies in 14 communities in Abuja, Nigeria. Six hundred and ninety-one (341 females, 350 males) individuals participated in this study. We analyzed the response ratio, relative increase, and sample collection time. The potential treatment uptake and change in social behavior were determined based on a semi-structured questionnaire. The mean response ratio of the image-based strategy was 89.7% representing a significantly higher ratio than the 27.8%, which was observed under the standard mobilization approach (p ≤ 0.001). The image-based method was associated with 100% of the participants agreeing to provide urine samples, 94% willing to be treated, 89% claiming to have been invited to participate in the study by a friend, and 91% desiring to change a predisposing behavioral habit. These findings indicate that image-based community awareness campaigns may increase the population's perception about schistosomiasis transmission and treatment. This raises new possibilities for local resource mobilization to expand services in reaching the last mile in schistosomiasis control.

Towards Inclusive Diagnostics for Neglected Tropical Diseases: User Experience of a New Digital Diagnostic Device in Low-Income Settings.

Designing new and inclusive diagnostic tools to detect Neglected Tropical Diseases (NTDs) to achieve rational disease control requires a co-design process where end-users' input is important. Failure to involve all potential end-users in new diagnostics for NTDs can result in low use and adoption failure, leading to persistent infection hot spots and ineffective disease control. There are different categories of potential end-users of new diagnostic tools for NTD control, and it is unclear if there are differences between the user efficiency, effectiveness, perception, and acceptability across these end-user categories. This study evaluated the usability, user perception, contextual factors affecting the user's experience, and acceptability of a new digital optical diagnostic device for NTDs across three types of potential end users. A total of 21 participants were tested. Laboratory scientists, technicians, and Community Health Extension Workers (CHEWs) in training achieved similar scores on the usability and user perception questionnaires with no statistically significant difference between end-user categories. All participants also have high scores for the user perception domains which strongly correlate with the acceptability of the AiDx NTDx Assist device. This study indicates that, by providing digital diagnostic tools in combination with minimal training and support, CHEWs undergoing training and, by extension, CHEWs post-training, can be involved in the diagnoses of NTDs, potentially enhancing a community's capabilities to diagnose, treat, and control NTDs.

A review on innovative optical devices for the diagnosis of human soil-transmitted helminthiasis and schistosomiasis: from research and development to commercialization.

Diagnosis of soil-transmitted helminth (STH) and schistosome infections relies largely on conventional microscopy which has limited sensitivity, requires highly trained personnel and is error-prone. Rapid advances in miniaturization of optical systems, sensors and processors have enhanced research and development of digital and automated microscopes suitable for the detection of these diseases in resource-limited settings. While some studies have reported proof-of-principle results, others have evaluated the performance of working prototypes in field settings. The extensive commercialization of these innovative devices has, however, not yet been achieved. This review provides an overview of recent publications (2010­2022) on innovative field applicable optical devices which can be used for the diagnosis of STH and schistosome infections. Using an adapted technology readiness level (TRL) scale taking into account the WHO target product profile (TPP) for these diseases, the developmental stages of the devices were ranked to determine the readiness for practical applications in field settings. From the reviewed 18 articles, 19 innovative optical devices were identified and ranked. Almost all of the devices (85%) were ranked with a TRL score below 8 indicating that, most of the devices are not ready for commercialization and field use. The potential limitations of these innovative devices were discussed. We believe that the outcome of this review can guide the end-to-end development of automated digital microscopes aligned with the WHO TPP for the diagnosis of STH and schistosome infections in resource-limited settings.

Performance Evaluation of the Schistoscope 5.0 for (Semi-)automated Digital Detection and Quantification of Schistosoma haematobium Eggs in Urine: A Field-based Study in Nigeria.

Conventional microscopy is the standard procedure for the diagnosis of schistosomiasis, despite its limited sensitivity, reliance on skilled personnel, and the fact that it is error prone. Here, we report the performance of the innovative (semi-)automated Schistoscope 5.0 for optical digital detection and quantification of Schistosoma haematobium eggs in urine, using conventional microscopy as the reference standard. At baseline, 487 participants in a rural setting in Nigeria were assessed, of which 166 (34.1%) tested S. haematobium positive by conventional microscopy. Captured images from the Schistoscope 5.0 were analyzed manually (semiautomation) and by an artificial intelligence (AI) algorithm (full automation). Semi- and fully automated digital microscopy showed comparable sensitivities of 80.1% (95% confidence interval [CI]: 73.2-86.0) and 87.3% (95% CI: 81.3-92.0), but a significant difference in specificity of 95.3% (95% CI: 92.4-97.4) and 48.9% (95% CI: 43.3-55.0), respectively. Overall, estimated egg counts of semi- and fully automated digital microscopy correlated significantly with the egg counts of conventional microscopy (r = 0.90 and r = 0.80, respectively, P < 0.001), although the fully automated procedure generally underestimated the higher egg counts. In 38 egg positive cases, an additional urine sample was examined 10 days after praziquantel treatment, showing a similar cure rate and egg reduction rate when comparing conventional microscopy with semiautomated digital microscopy. In this first extensive field evaluation, we found the semiautomated Schistoscope 5.0 to be a promising tool for the detection and monitoring of S. haematobium infection, although further improvement of the AI algorithm for full automation is required.

Large volume holographic imaging for biological sample analysis.

SIGNIFICANCE: Particle field holography is a versatile technique to determine the size and distribution of moving or stationary particles in air or in a liquid without significant disturbance of the sample volume. Although this technique is applied in biological sample analysis, it is limited to small sample volumes, thus increasing the number of measurements per sample. In this work, we characterize the maximum achievable volume limit based on the specification of a given sensor to realize the development of a potentially low-cost, single-shot, large-volume holographic microscope. AIM: We present mathematical formulas that will aid in the design and development and improve the focusing speed for the numerical reconstruction of registered holograms in particle field holographic microscopes. Our proposed methodology has potential application in the detection of Schistosoma haematobium eggs in human urine samples. APPROACH: Using the Fraunhofer holography theory for opaque objects, we derived an exact formula for the maximum diffraction-limited volume for an in-line holographic setup. The proof-of-concept device built based on the derived formulas was experimentally validated with urine spiked with cultured Schistosoma haematobium eggs. RESULTS: Results obtained show that for urine spiked with Schistosoma haematobium eggs, the volume thickness is limited to several millimeters due to scattering properties of the sample. The distances of the target particles could be estimated directly from the hologram fringes. CONCLUSION: The methodology proposed will aid in the development of large-volume holographic microscopes.

Imaging & identification of malaria parasites using cellphone microscope with a ball lens.

We have optimized the design and imaging procedures, to clearly resolve the malaria parasite in Giemsa-stained thin blood smears, using simple low-cost cellphone-based microscopy with oil immersion. The microscope uses a glass ball as the objective and the phone camera as the tube lens. Our optimization includes the optimal choice of the ball lens diameter, the size and the position of the aperture diaphragm, and proper application of immersion, to achieve diagnostic capacity in a wide field of view. The resulting system is potentially applicable to low-cost in-the-field optical diagnostics of malaria as it clearly resolves micron-sized features and allows for analysis of parasite morphology in the field of 50 × 50 µm, and parasite detection in the field of at least 150 × 150 µm.

Optical path difference microscopy with a Shack-Hartmann wavefront sensor.

In this Letter, we show that a Shack-Hartmann wavefront sensor can be used for the quantitative measurement of the specimen optical path difference (OPD) in an ordinary incoherent optical microscope, if the spatial coherence of the illumination light in the plane of the specimen is larger than the microscope resolution. To satisfy this condition, the illumination numerical aperture should be smaller than the numerical aperture of the imaging lens. This principle has been successfully applied to build a high-resolution reference-free instrument for the characterization of the OPD of micro-optical components and microscopic biological samples.

Aliasing, coherence, and resolution in a lensless holographic microscope.

We have shown that the maximum achievable resolution of an in-line lensless holographic microscope is limited by aliasing and, for collimated illumination, cannot exceed the camera pixel size. This limit can be achieved only when the optimal conditions on the spatial and temporal coherence state of the illumination are satisfied. The expressions defining the configuration, delivering maximum resolution with given spatial and temporal coherence of the illumination, are obtained. The validity of these conditions is confirmed experimentally.