Background: Schistosomiasis (SCH) and soil transmitted helminthiasis (STH) have been targeted for elimination as a public health problem (EPHP) within the World Health Organization (WHO)’s Roadmap for Neglected Tropical Diseases (NTDs) 2021–2030. One of the global strategies for the control and elimination of these diseases is the mass administration of praziquantel and albendazole/mebendazole without prior individual diagnosis. To measure the progress towards the 2030 target, we conducted an assessment to determine the impact of the 3–5 rounds of annual mass drug administration among school age children in Ekiti State. Such scientific insights into the impact of these treatments will facilitate improved planning and targeting of resources towards reaching the last mile. Methodology: This assessment was conducted in 16 local government areas (LGAs) of Ekiti State between October and November 2023. Samples were collected from pupils in 166 primary and junior secondary schools across 166 wards of the State. Urine and stool samples were collected from 7670 pupils of ages 5 to 14 years, following standard laboratory procedures. Urine membrane filtration techniques were used for urine preparation while the Kato–Katz technique was used for stool preparation. A novel AiDx digital microscope was used to examine the presence of any ova in the prepared specimen. Parasite ova in urine were reported as the number of ova/10 mL of urine, and were categorized as light infection (˂50 ova/10 mL of urine) or heavy infection (>50 ova/10 mL of urine) while ova of parasites in stool samples were reported as eggs per gram of stool (EPG) and categorized into light, moderate and heavy infection. Results: Overall, 0.76% (0.56–0.95) at 95% CI of the 7670 respondents were infected with Schistosomia haematobium. No Schistosoma mansoni infection was recorded in the study. Similarly, 3.9% (3.43–4.29) at 95% CI were infected with STHs. The overall prevalence of schistosomiasis had significantly reduced from 8.2% in 2008 to 0.8%, while the overall prevalence of STHs significantly reduced from 30.9% to 3.9% with Ascaris lumbricoides being the dominant species of STH. In the 16 LGAs assessed, Ekiti West had the highest S. haematobium prevalence of 4.26%. Ise/Orun and Oye ranked second and third with a prevalence of 3.48% and 2.40% respectively, while all other LGAs had <1% prevalence. The prevalence of STHs was highest in Ekiti-West with a prevalence of 10.45% while Emure and Ikole Local Governments had the lowest prevalence of 0.31% and 0.38%, respectively. There was no significant difference in the prevalence of schistosomiasis between male (0.76%) and female (0.75%) as p ≥ 0.05. Similarly, the difference in prevalence for STH among males (3.95%) was not significantly different from their female counterparts (3.77%), p ≥ 0.05. Conclusions: Based on the WHO guidelines, this study demonstrated that only three LGAs require continued MDA every 2/3 years, seven require only surveillance while six are now non-endemic for schistosomiasis. Similarly, two of the LGAs require one round of MDA yearly, eight LGAs need one round of MDA every two to three years and six LGAs are now below the treatment threshold and no longer require treatment for STH. ... Read more

In this work, we developed an automated system for the detection and classification of soil-transmitted helminths (STH) and Schistosoma (S.) mansoni eggs in microscopic images of fecal smears. We assembled an STH and S. mansoni dataset comprising over 3,000 field-of-view (FOV) images containing parasite eggs, extracted from more than 300 fecal smear prepared using the Kato-Katz technique. These images were acquired using Schistoscope—a cost-effective automated digital microscope. After annotating the STH and S. mansoni eggs, we employed a transfer learning approach to train an EfficientDet deep learning model, using 70% of the dataset for training, 20% for validation, and 10% for testing. The developed model successfully identified STH and S. mansoni eggs in the FOV images, achieving weighted average scores of Precision, Sensitivity, Specificity, and F-Score across four classes of helminths (A. lumbricoides, T. trichiura, hookworm, and S. mansoni). Our system highlights the potential of the Schistoscope, enhanced with artificial intelligence, for detecting STH and S. mansoni infections in remote, resource-limited settings and for supporting the monitoring and evaluation of neglected tropical disease (NTD) control programs. ... Read more

Introduction: One of the global strategies for the elimination of schistosomiasis is by Mass Drug Administration (MDA) of a single oral dose of praziquantel (40 mg/kg) without a prior individual diagnosis, with a target of >75% treatment coverage among school-aged children. This study was conducted to determine the endemicity of schistosomiasis among school-aged children and adults in Abuja, Nigeria. Methods: A total of 1370 participants were recruited, which consisted of 667 (48.67%) males and 703 (51.31%) females. Urine and stool specimens were collected from each participant and analyzed using standard procedures. Results: The overall prevalence of schistosomiasis was 27.5% in this study with Abuja Municipal having the highest prevalence of 49%, while the least (6.1%) was reported in Bwari LAC. The prevalence of schistosomiasis significantly differs (p < 0.05) between the area councils. The location of communities significantly affected the prevalence of schistosomiasis in Abaji, AMAC, and Gwagwalada LACs (p < 0.005). The Schistosoma recovered in this study were S. haematobium and S. mansoni. The prevalence of schistosomiasis increased from the baseline of 21.1% to 49% in Gwagwalada LAC. Gender significantly affected the prevalence of schistosomiasis as more males were infected (33.1%) than their female counterparts (22.2%) (p < 0.05). The prevalence of schistosomiasis was 31% and 23.9% among SAC and adults, respectively. The participants’ activities in the river significantly affected the prevalence of schistosomiasis in this study (p < 0.05). Conclusions: The clamour for urgent government and non-government intervention through alternate sources of water like boreholes or pipe-borne water, as well as implementing a behavioural change campaign across the communities to prevent the recurrence, are advocated. ... Read more

Traditionally, automated slide scanning involves capturing a rectangular grid of field-of-view (FoV) images which can be stitched together to create whole slide images, while the autofocusing algorithm captures a focal stack of images
to determine the best in-focus image. However, these methods can be timeconsuming due to the need for X-, Y- and Z-axis movements of the digital microscope while capturing multiple FoV images. In this paper, we propose a solution to minimise these redundancies by presenting an optimal procedure for automated slide scanning of circular membrane filters on a glass slide. We achieve this by following an optimal path in the sample plane, ensuring that only FoVs overlapping the filter membrane are captured. To capture the best infocus FoV image, we utilise a hill-climbing approach that tracks the peak of the mean of Gaussian gradient of the captured FoVs images along the Z-axis. We implemented this procedure to optimise the efficiency of the Schistoscope, an automated digital microscope developed to diagnose urogenital schistosomiasis by imaging Schistosoma haematobium eggs on 13 or 25 mm membrane filters. Our improved method reduces the automated slide scanning time by 63.18%and 72.52% for the respective filter sizes. This advancement greatly supportsthe practicality of the Schistoscope in large-scale schistosomiasis monitoringand evaluation programs in endemic regions. This will save time, resources andalso accelerate generation of data that is critical in achieving the targets for schistosomiasis elimination. ... Read more

Community mobilisation is a vital process for raising awareness and increasing participation in healthcare interventions, research, and programmes that require human sample collection and mass management. In this report, we present the community mobilisation approach undertaken for the implementation of the operational mapping and assessment of granular schistosomiasis and soil-transmitted helminths in Ekiti State, Nigeria. The mobilisation was conducted in 177 communities/wards of the 16 local government areas. A total of 15,340 urine and stool samples were collected in 34 days. The efficacy and success of the strategy were evaluated through the following three performance metrics: community compliance rate, the participant response rate at the community level, and the overall compliance response rate of the four most sensitive LGAs. Community compliance was 93.7% as sample collection was denied in nine communities and two other communities demanded the return of the collected samples despite our mobilisation effort because of cultural bias and myths that connect the collection of stool and urine samples to ritual activities in the local context. The participant response rate at the community level was 86.7%. Three of the four sensitive LGAs (based on previous assessment programmes) demonstrated satisfactory compliance rates of 100%, while a response rate of 64.0% was computed for one of the LGAs. We believe our approach contributed to effective community mobilisation and awareness and that the developed model has the potential to improve participation rates in large healthcare assessments and intervention programmes. ... Read more

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. ... Read more

A growing awareness of health as a human right, mainly in low- and middle-income countries, is promoting universal health access for increasing numbers of people. Universal access to health to a large extent depends on access to medical equipment and medical staff. In this chapter, we focus on the access to medical equipment, more specifically, equipment for diagnostics and how frugal innovation and distributed manufacturing can contribute to an increase of access to these devices. We present a case study of a frugal design for a centrifuge for sample preparation for schistosomiasis. This neglected tropical disease impacts the lives of over 240 million people, mainly in sub-Saharan Africa ... Read more

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. ... Read more

Purpose: Automated diagnosis of urogenital schistosomiasis using digital microscopy images of urine slides is an essential step toward the elimination of schistosomiasis as a disease of public health concern in Sub-Saharan African countries. We create a robust image dataset of urine samples obtained from field settings and develop a two-stage diagnosis framework for urogenital schistosomiasis.

Approach: Urine samples obtained from field settings were captured using the Schistoscope device, and S. haematobium eggs present in the images were manually annotated by experts to create the SH dataset. Next, we develop a two-stage diagnosis framework, which consists of semantic segmentation of S. haematobium eggs using the DeepLabv3-MobileNetV3 deep convolutional neural network and a refined segmentation step using ellipse fitting approach to approximate the eggs with an automatically determined number of ellipses. We defined two linear inequality constraints as a function of the overlap coefficient and area of a fitted ellipses. False positive diagnosis resulting from over-segmentation was further minimized using these constraints. We evaluated the performance of our framework on 7605 images from 65 independent urine samples collected from field settings in Nigeria, by deploying our algorithm on an Edge AI system consisting of Raspberry Pi + Coral USB accelerator.

Result: The SH dataset contains 12,051 images from 103 independent urine samples and the developed urogenital schistosomiasis diagnosis framework achieved clinical sensitivity, specificity, and precision of 93.8%, 93.9%, and 93.8%, respectively, using results from an experienced microscopist as reference.

Conclusion: Our detection framework is a promising tool for the diagnosis of urogenital schistosomiasis as our results meet the World Health Organization target product profile requirements for monitoring and evaluation of schistosomiasis control programs.
... Read more

To achieve the WHO’s goal of sustained elimination of Lymphatic Filariasis disease, there is the need for accurate diagnostic device especially in areas of low-intensity infections. This project, which is a collaboration of the Nigerian Federal Ministry of Health (FMoH), AiDx and funded by THE END FUND is exploring the performance capacity of the novel AiDx_NTDx Assist automated microscope in the detection of microfilaria – Wuchereria bancrofti in prepared blood samples (glass slides) using standard microscopy as a reference. The prevalence of circulating Wuchereria bancrofti microfilaria in blood was assessed using automated Image based microscopy analysis for the detection of microfilariae in prepared blood smears.

1250 people in four LGAs of Ogun state, Nigeria participated in this study. All prepared blood samples analyzed by both expert manual microscopy and the AiDx NTDx Assist results showed that none of the 1250 participants samples analyzed had any presence of W. bancrofti microfilariae in their blood. Since no positive samples was detected by the reference test and the AiDx NTDx Assist, it was impossible to estimate the sensitivity of the device. However, based on the negative results obtained, the AiDx NTDx Assist showed a specificity of 100%, an accuracy of 100% and a Negative Predictive Value of 100%.

Despite the baseline report obtained from the National data base of the ministry of health, indicating the prevalence of 10%, 8.2%, 4.2% and 4% in the four local government areas where samples were collected, we were not able to find a participant with detectable microfilaria. Evaluation of the AiDx NTDx Assist device shows direct correlation with the expert manual microscopy. Although samples were taken in remote/rural areas of some of the LGA, e.g., Adodo Ota, result obtained however suggest a deviation from baseline and reality. This may be due to previous MDA undertaken in 2018 as reported by the state NTD officers. Further, thorough reassessment is therefore recommended . ... Read more

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 (2010-2022) 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. ... Read more

For many parasitic diseases, the microscopic examination of clinical samples such as urine and stool still serves as the diagnostic reference standard, primarily because microscopes are accessible and cost-effective. However, conventional microscopy is laborious, requires highly skilled personnel, and is highly subjective. Requirements for skilled operators, coupled with the cost and maintenance needs of the microscopes, which is hardly done in endemic countries, presents grossly limited access to the diagnosis of parasitic diseases in resource-limited settings. The urgent requirement for the management of tropical diseases such as schistosomiasis, which is now focused on elimination, has underscored the critical need for the creation of access to easy-to-use diagnosis for case detection, community mapping, and surveillance. In this paper, we present a low-cost automated digital microscope—the Schistoscope—which is capable of automatic focusing and scanning regions of interest in prepared microscope slides, and automatic detection of Schistosoma haematobium eggs in captured images. The device was developed using widely accessible distributed manufacturing methods and off-the-shelf components to enable local manufacturability and ease of maintenance. For proof of principle, we created a Schistosoma haematobium egg dataset of over 5000 images captured from spiked and clinical urine samples from field settings and demonstrated the automatic detection of Schistosoma haematobium eggs using a trained deep neural network model. The experiments and results presented in this paper collectively illustrate the robustness, stability, and optical performance of the device, making it suitable for use in the monitoring and evaluation of schistosomiasis control programs in endemic settings. ... Read more

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 (r50.90 and r50.80, 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. ... Read more

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. ... Read more

Fourier Ptychography is a computational imaging technique able to decouple high resolution from wide field of view, bypassing the diffraction limit of the microscope. Since it does not rely on high precision mechanics or fluorescent imaging, it is of practical interest for implementation in low scale devices. Despite its gains, realizing a functional low-cost setup working at the theoretical limits is challenging due to many factors causing discrepancies between theory and practice. Misalignment of the light emitting diode array (LED-array), optical system aberrations and use of partial coherent sources are common issues which have been addressed with calibration algorithms. However, physical interpretation of how these factors influence the algorithm and cause mismatches between theory and practice has had little attention so far. This work provides a discussion based on simulation results on the effect of the partial coherence of the source. From obtained results, an optimal set of LEDs for data acquisition is described which avoids degeneracy caused by partial coherence and is based on the numerical aperture (NA) of the objective and source parameters such as bandwidth and size. ... Read more

Schistosomiasis is a neglected tropical disease of Public Health importance affecting over 252 million people worldwide with Nigeria having a very high number of cases. It is caused by blood flukes of the genus Schistosoma and transmitted by freshwater snails. To achieve the current global elimination objectives, low-cost and easy-to-use diagnostic tools are critically needed. Recent innovations in optical and computer technologies have made handheld digital and smartphone-based microscopes a viable diagnostic approach. Development, validation and deployment of these diagnostic devices for field use, however, require the optimisation of its optical train for the registration of high-resolution images and the realisation of a robust system design that can be locally produced in low-income countries. Field research conducted in Nigeria with active involvement of key stakeholders in research and development (RD) led to the design of an initial prototype device for the diagnosis of urinary schistosomiasis, called Schistoscope 1.0. In this paper, we present further development of the Schistoscope 1.0 along two parallel design trajectories: A Raspberry Pi and a Smartphone-based Schistoscope. Specifically, we focused on the optimization of the optics, embodiment design and the electronics systems of the devices so as to produce a robust design with potential for local production. ... Read more

We present a simple method for the diagnosis of urinary schistosomiasis using an in-line lensless holographic microscope combined with flow cytometry technique. Using simple image processing algorithms and binary image classifier, our system provides automated detection of Schistosoma haematobium eggs in infected urine samples. Registered hologram is reconstructed by applying backpropagation from sensor to sample plane and reconstructed image is automatically analysed for the presence of S. haematobium eggs. Designed for use in a resource-poor laboratory setting, our proposed method has been implemented using a Raspberry Pi computer. From pre-clinical test performed with human urine samples spiked with S. haematobium eggs (approximately 200 eggs per 12 ml of urine), we achieved a sensitivity and specificity of 50.6% and 98.6% respectively. Our proposed method requires no complex sample preparation methods making the system simple to operate and useable in point-of-care diagnosis of urinary schistosomiasis.This method can be optimized to complement existing diagnostic procedures for the detection of S. haematobium eggs and can be deployed to inaccessible remote areas. ... Read more

Malaria remains an important cause of high morbidity and mortality worldwide. According to World Health Organisation (WHO) malaria report for 2017, malaria accounted for the death of 435,000 people. It is the leading cause of death among pregnant women and little children. 11% of maternal and 20% of under–five deaths are attributed to malaria every year. Malaria transmission is currently active in 95 countries putting the lives of 3.2 billion people at risk. 40% of the malaria related deaths are linked to Nigeria and the Democratic republic of the Congo. Since malaria symptoms are generally non-specific and usually overlap with the symptoms of other febrile illnesses, clinical diagnosis are typically presumptive and often results into high number of false positives which potentially lead to the abuse of antimalarial drugs. The consistent abuse of antimalarial drugs has produced the consequent effect of drug resistance which is a major concern in the current global malaria control and elimination efforts. The WHO therefore recommends that an effective malaria case management plan must be predicated on a standard parasite-based confirmatory diagnostic test. Conventional light microscopy is the recommended reference diagnostic standard prescribed by the World Health Organisation. This method is particularly of interest because it allows parasite specie differentiation, quantification of the parasite density in a given blood smear, high accuracy (although this depends on the expertise of the microscopist), low direct cost, visualization of different stages of the parasite development etc. While well-equipped laboratories for malaria diagnosis are commonly available in developed urban and peri-urban areas, low-resource settings of malaria endemicity usually have very limited options. The recommended standard microscopy is less accessible in resource-limited settings because of the following: lack of required technical skills, incessant power outages, lack of efficient maintenance capability, delayed diagnosis due to intense workload, inaccuracies due to manual counting of the parasites detected in the blood film etc. The inaccuracies of parasite density estimation eventually affects the accuracy and efficiency of the prescribed treatment which could have fatal consequences. A diagnostic process is termed inconclusive by the WHO until and unless a minimum of 100 measurement (microscopy examination of 100 high powered-fields) has been done on a prepared thick blood film. For a thin blood film which provides more details about the morphology of the parasite, an average of 800 measurement is required. This is an easy task for laboratory technologist in malaria non-endemic countries where an average of 120 malaria cases occur yearly. But for malaria endemic country where several thousand cases are reported daily, this is by no means a mean task as it demands full concentration, time, high expertise and experience. To realize current global effort to reduce the heavy malaria burden, the need for a reliable, efficient, accurate and automated point-of-care diagnostic tool cannot be overemphasized. The focus of this thesis work therefore, is to develop smart optical methods that alleviate the burden of manual microscopy by researching methods to optimise existing imaging modalities which can be integrated with smart algorithms for quick malaria parasite detection in infected patients. Aside malaria, schistosomiasis is the second most common parasitic diseases. Although it falls into the category of a Neglected Tropical Disease (NTD), 220.8 million people required preventive treatment in the year 2017 according to the World Health Organisation report. It is a disease of the poor and it is prevalent in tropical and subtropical areas and particularly common in communities where there is no access to clean drinking water and proper sanitation. 779 million people are at risk of contracting this disease which results into impaired growth and development, diminished physical fitness, bladder cancer and decreased neurocognitive abilities. Although safe and effective medication is widely available for treatment, accurate diagnostic techniques for schistosomiasis is hugely underdeveloped and remains a critical challenge. Intestinal and urogenital schistosomiasis are the two variants of this Neglected tropical disease but in this research, we focus on urogenital schistosomiasis (caused by S. haemtobium) because it is most prevalent among the population we worked with and also because it is easier to detect in urine. The diagnostic protocol for S. haemtobium prescribes urine filtration with WHO recommended standard membrane filters (with 12 μl pore size). Several critical measurements by an expert must be done to detect the targeted foreign bodies (parasite eggs) in the urine samples before a reliable conclusion can be made. Also for a confirmatory diagnosis, it is standard practice to examine different samples collected from the patient at different specific intervals. This is particularly recommended to increase the amount of sample analysis per patient thereby increasing the sensitivity of the test. Since this process involves the microscopy examination of filtered urine samples, it is also limited by the challenges already described for standard malaria microscopy. Although several antigen and antibody based rapid diagnostic test kits have been developed for both malaria and schistosomiasis, the reliability of the performance of these diagnostic test is still a major concern. This thesis is aimed at the development of reliable, robust, accurate, cost effective and easy-to-use point-of-care optical devices for quick diagnosis of malaria and urogenital disease in human samples. This thesis begins by looking at light microscopy with extended depth of field. Wavefront coding with adaptive optics and digital inline holography have been considered in this work. An optimal configuration that guarantees maximum resolution based on the coherence property of illuminating source and the specification of the imaging sensor is prescribed. In this system, interference of a plane and object wave at the detector plane generates a hologram from which the complex amplitude of the field in the object plane can be numerically reconstructed by solving an inverse source problem. This method is of practical interest particularly because unlike the conventional microscope, details in transparent biological samples can be retrieved since both amplitude and the phase of the field is reconstructed. It provides potential solution towards label-free diagnosis of parasitic diseases. Combined with flow cytometry and data-driven algorithms we applied this methodology to the development of rapid detection of S. haemtobium. A working prototype device with the potential to map the diseases has been developed and tested on the field. The system design takes into consideration practical field conditions such as ease-of-use, cost, harsh environmental conditions, erratic power outages, system robustness against dust and other artifacts. Feedbacks and results from the field are very promising. Leveraging on recent advances in cellphone and 3-D printing technologies we developed an automated cell-phone based microscope towards the realization of a rapid point-of-care diagnosis of malaria. The challenge here is to optimise the optical train of a low-cost commonly available cell-phone to detect malaria parasite with sufficient resolution. It was found that existing cell-phone based microscope could not resolve the 1 µm size malaria parasites because of the system optical aberration and the numerical aperture limit of the phone objectives. Although this method demonstrate the capability of the cell phone based microscope to image malaria parasite, however the achievable field of view is limited to 150 × 150 µm. This implies that over 600 measurement is needed for a conclusive diagnosis. We circumvent this limitation by the novel implementation of computer-assisted dry fluorescent microscopy. Using computational analysis of image containing large number of blood cells, we establish a robust statistics which provides reliable diagnostic recommendation. The technique was tested with in vitro and in vivo samples and has demonstrated its suitability for highly sensitive, robust and automated diagnostics of malaria. It requires minimal human intervention, uses simple sample preparation, provides high degree of independence of expert judgement, and has a potential for massive community screening for malaria control and elimination programs. The design specifications for the development of working prototypes presented in this thesis took into account feedbacks from diagnostic experts from the following non-governmental organisations: Doctors without Borders, Malaria Consortium, AMREF, Save the Children and Christian Aid (Nigeria). Also, our methodology was thoroughly validated by discussions and interactions with experts on the field (in Nigeria, Ivory Coast, Gabon, Uganda and Ghana) and with parasitologists, researchers and vaccine developers in the Netherlands, Spain, Ireland and Germany, leading to valuable new insights.”
It is our goal that the diagnostic methods and prototype presented in this thesis will be used to compliment the limitations of the existing diagnostic techniques.
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Schistosomiasis is a treatable and preventable neglected tropical disease of Public Health importance affecting over 200 million people worldwide while Nigeria is one of the high burden countries. Currently, available diagnostic tests are cumbersome, low in sensitivity and not field-adaptable given the high skills required that are not available in the rural settings where the diseases are majorly prevalent. There is an urgent need for an easy to use automated diagnostic device to replace the current gold standard, the human-operated microscope. Many promising automated diagnostic technologies are under development. However, a good understanding of the real needs within the local healthcare context is crucial in order to develop and implement a new health diagnostic device. Too often, there is a mismatch between what is needed and what is developed. A target product profile can guide the R&D process in matching with the needs in the local healthcare context. The goal of this project is to combine gaps in the healthcare system and needs from stakeholders with technological possibilities in order to develop a target product profile for a diagnostic device for S. haematobium for specific healthcare scenarios in Nigeria. ... Read more