Automated Detection of Malarial Retinopathy in Digital Fundus Images for Improved Diagnosis in Malawian Children with Clinically Defined Cerebral Malaria

Cerebral malaria (CM), a complication of malaria infection, is the cause of the majority of malaria-associated deaths in African children. The standard clinical case definition for CM misclassifies ~25% of patients, but when malarial retinopathy (MR) is added to the clinical case definition, the specificity improves from 61% to 95%. Ocular fundoscopy requires expensive equipment and technical expertise not often available in malaria endemic settings, so we developed an automated software system to analyze retinal color images for MR lesions: retinal whitening, vessel discoloration, and white-centered hemorrhages. The individual lesion detection algorithms were combined using a partial least square classifier to determine the presence or absence of MR. We used a retrospective retinal image dataset of 86 pediatric patients with clinically defined CM (70 with MR and 16 without) to evaluate the algorithm performance. Our goal was to reduce the false positive rate of CM diagnosis, and so the algorithms were tuned at high specificity. This yielded sensitivity/specificity of 95%/100% for the detection of MR overall, and 65%/94% for retinal whitening, 62%/100% for vessel discoloration, and 73%/96% for hemorrhages. This automated system for detecting MR using retinal color images has the potential to improve the accuracy of CM diagnosis

Retinopathy in severe malaria in Ghanaian children - overlap between fundus changes in cerebral and non-cerebral malaria

<p>Abstract</p> <p>Background</p> <p>In malaria-endemic areas, reliably establishing parasitaemia for diagnosis of malaria can be difficult. A retinopathy with some features unique to severe malaria with a predictive value on prognosis, has been described. Detection of this retinopathy could be a useful diagnostic tool. This study was designed to determine the diagnostic usefulness of retinopathy on ophthalmoscopy in severe malaria syndromes: Cerebral malaria (CM) and non-cerebral severe malaria (non-CM), i.e. malaria with respiratory distress (RD) and malaria with severe anaemia (SA), in Ghanaian children. Secondly, to determine any association between retinopathy and the occurrence of convulsions in patients with CM.</p> <p>Methods and subjects</p> <p>A cross-sectional study of consecutive patients on admission with severe malaria who were assessed for retinal signs, at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, from July to August 2002 was done. All children had dilated-fundus examination by direct and indirect ophthalmoscopy.</p> <p>Results</p> <p>Fifty-eight children aged between six months and nine years were recruited. Twenty six(45%) had CM, 22 with convulsion; 26(45%) had SA and six(10%) had RD.</p> <p>Any retinopathy was seen in: CM 19(73%), SA 14(54%), RD 3(50.0%), CM with convulsion 15(68%) and CM without convulsion 4(100%). Comparison between CM versus non-CM groups showed a significant risk relationship between retinal whitening and CM(OR = 11.0, CI = 2.2- 56.1, p = 0.001). There was no significant association with papilloedema(OR = 0.9, CI = 0.3 - 3.0, p = 0.9), macular whitening(OR = 1.6, CI = 0.5 - 4.8, p = 0.4), macular haemorrhage(OR = 0.28, CI = 0.03 - 2.7 p = 0.2), retinal haemorrhage(OR = 1.9, CI = 0.6 - 5.6, p = 0.3), vessel abnormality(OR = 1.9, CI = 0.6 - 6.1, p = 0.3) and cotton wool spots(OR not calculated, p = 0.08).</p> <p>Tortuous and engorged retinal veins, not previously described as a feature of CM, was the most common vascular abnormality(15/58 = 26%) and was detected even in the absence of papilloedema.</p> <p>Conclusion</p> <p>Retinal whitening, a sign suggestive of retinal ischaemia, was significantly more common in CM than in non-CM syndromes. However, the high prevalence of any retinopathy in the latter suggests that the brain and the retina may be suffering from ischaemia in both CM and non-CM.</p

Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina

Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with P. falciparum cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n = 817, OR, 95% CI: 2.90, 1.96–4.30; 3.4, 1.8–6.3, both p<0.001), and arteriolar involvement by intravascular filling defects (angiographic image analysis, n = 260, 2.81, 1.17–6.72, p<0.02) were strongly associated with death. Orange vessels had dense sequestration of late stage parasitised red cells (histopathology, n = 29; sensitivity 0.97, specificity 0.89) involving 360° of the lumen circumference, with altered protein expression in blood-retinal barrier cells and marked loss/disruption of pericytes. Retinal whitening was topographically associated with tissue response to hypoxia. Severe neurovascular sequestration is visible at the bedside, and is a marker of severe disease useful for diagnosis and management

A Comparative Study of the Pathology and Pathophysiology of Severe Malaria in a Non-Human Primate Model

With the rise in plasmodial drug resistance throughout the world, a dwindling arsenal of anti-malarials and a predilection for use of less than ideal murine models, the need for effective, applicable and established animal models through which to understand severe malarial disease and test potential treatments is becoming increasingly crucial. Plasmodium coatneyi was discovered in the Philippines in the early 1960s in Rhesus macaque monkeys and has been evaluated sporadically as a potential platform for comparative studies of Plasmodium falciparum induced severe and cerebral malaria in humans. Using 30 years worth of archival samples at the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, compounded with data and material from a series of prospective experimental studies, the work in this thesis sought to fully characterize and describe the pathology and pathobiology of the P. coatneyi/Rhesus macaque model. This included a thorough examination of the parasite host interaction, clinical symptomology, hematology and clinical pathology, gross pathology, histopathology, immunohistochemistry, cerebrospinal fluid cytokine profiles, transmission and scanning electron microscopy and atomic force microscopy of the disease in 45 adult rhesus macaques. The study further compared P. coatneyi with existing P. falciparum infected human material maintained at the National University of Singapore’s Vivax laboratory and Oxford University’s Ultrastructural Morphology Group, Nuffield Division of Clinical Laboratory Sciences. The study culminated in a successful clinical drug trial which evaluated the efficacy of varying doses of methylene blue as a radical cure for malaria in this non-human primate model. In many ways, the model mirrors P. falciparum, however the benefit of this evaluation is that it highlights not only the similarities but also the divergences. The successful completion of this description of the pathology and pathobiology of the P. coatneyi/Rhesus macaque model of severe and cerebral malaria adds a complex but effective animal model to the armamentarium in the ongoing war against malaria

BIOMARKERS AND PROGNOSTIC SCORING IN CEREBRAL MALARIA

Malaria remains a public health concern and remain the deadliest in infectious disease in the world. Cerebral malaria is a particularly severe complication of this disease and associated with high mortality. This literature review is made up from 19 literatures consisting of journals, and book. The literature review used data base www.pubmed.com, and www.scholar.google.com using “cerebral malaria and biomarker, predictor of cerebral malaria and treatment of severe malaria”. The languages for this journal are English and Indonesian. From the collection of literatures in this literature review, severe consists of cerebral malaria, blackwater fever, acute kidney injury, pulmonary edema, electrolyte disturbance, hematology disturbance, and obstetrics emergency resulting from malaria which is postpartum hemorrhage. Cerebral malaria increases the mortality of the patient, so they have to be diagnosed early and treated precisely. Patients with infection of plasmodium falciparum and GCS<11 must be suspected as cerebral malaria. Biomarker examination such as Soluble ICAM-1, Specific muscle’s protein, Angiopoetin-1 and 2, and Plasma microparticles is the most precise way to detect malarial emergency earlier Coma Acidosis Malaria score is also found to be useful in predicting the prognosis in cerebral malaria. Early diagnosis should be made as early as possible to reduce mortality from malaria and its emergencies

Ocular Parasitic Infections – An Overview

Eyes are said to be the windows of body, by which this beautiful world is visualized. Human eye has a unique structure and is vulnerable to numerous infections. Whenever anatomical structures are breached, host defenses come into play, but if infection is severe and not treated timely, it could lead to visual impairment or blindness. Parasitic infections are considered, the significant causes of ophthalmic diseases worldwide. In this chapter, an overview of ocular parasitic infections (OPI) is detailed out, with an initial brief introduction followed by description of anatomy of the human eye and various defense mechanisms to provide better understanding of the parasitic infections affecting different parts of human eye. The last part includes individual details of various human ocular parasitic infections

Retinopathy and central nervous system microcirculatory abnormalities in adult cerebral malaria and their prediction of outcome

Introduction Malaria retinopathy is a set of visible changes in the retina which are specific to falciparum malaria. Studies to date have been mostly limited to comatose African children. Retinal changes in adults with severe malaria and severely unwell patients without malaria have been less well studied and the specificity, pathogenesis, diagnostic and prognostic value of malarial retinopathy in adults are not known. Methods A series of observational studies of retinopathy in Bangladesh, India and Malaysia were done from 2008-2012. The aims were to describe the spectrum of retinal changes in falciparum and knowlesi malaria in adults, determine their specificity for severe falciparum malaria, quantify the impact of malaria retinopathy on visual function, understand its pathogenesis and assess the potential contribution of retinopathy to confirming diagnosis of malarial coma, predicting prognosis and understanding pathogenesis of cerebral malaria. Results 495 patients were enrolled and underwent retinal photography (305 with P. falciparum malaria (112 cerebral, 68 noncerebral severe, 125 uncomplicated), 44 P. knowlesi, 43 sepsis, 41 encephalopathy and 62 healthy). Retinal whitening and white-centred haemorrhages were common and specific to severe falciparum malaria. Retinopathy was most common and severe in cerebral (88%) and fatal (91%) falciparum malaria. Moderate-severe retinopathy was 95% specific for cerebral malaria in comatose patients, and its severity correlated with depth of coma. Vessel whitening was not seen and papilloedema was rare. In noncerebral severe falciparum malaria, retinopathy predicted increased likelihood of later development of coma and death. Retinal findings in Bangladeshi children were similar to those in adults. Optic nerve sheath diameter was mildly increased and brain swelling minimal on MRI. Severity of retinopathy correlated with plasma lactate, serum bicarbonate, sequestered parasite load and red cell stiffness suggesting a central role for microvascular obstruction in the pathogenesis. Severity of retinal whitening correlated with decreased visual acuity. Conclusions Retinal changes seen in severe P. falciparum malaria in Asian adults is similar, but not identical, to that seen in African children. They have potential to help with diagnosis and prognosis of Asian adults with severe falciparum malaria. Microvascular obstruction is prominent in the pathogenesis of retinopathy and coma in adults whereas raised intracranial pressure is not

Cerebral malaria: a lethal complication of a common tropical infection

Cerebral malaria (CM) represents a deadly neurological complication associated with Plasmodium falciparum infection. It is defined as an unarousable coma or a deep level of unconsciousness in the presence of a P. falciparum parasitemia, the diagnosis confirmed after exclusion of other common causes of coma such as hypoglycemia, septicemia, metabolic derangements and bacterial and viral meningitis/encephalopathies. Mortality is high and some surviving patients sustain neuronal injury which manifests as long-term neuro-cognitive impairments. Microscopy of Giemsa-stained blood smears remains the gold standard for confirmation of malaria diagnosis. The purpose of this review was to summarize the updated knowledge on the disease, its presentation, complications and neurological sequelae and the presently available newer and experimental adjuvant therapies. For this review, a PubMed search was conducted for articles and case reports from 1968 to 2020 containing the keywords cerebral malaria, P. falciparum, neurological impairment, neurocognitive defects and artesunate combination therapy. The treatment includes specific antimalarial therapy, supportive therapy for multi-organ dysfunction and management of associated complications. Prompt and rapid stabilization of the patient, adequate fluid supplementation and correction of electrolyte imbalance remain the most vital supplementary interventions in these cases, along with early induction of primary parenteral antimalarial therapy in the form of artemisinin based combination therapy (ACT) or quinine. Neurological sequelae including seizures are frequently observed in many treated and recovered cases, with some patients having to endure long term neurocognitive defects