The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria.

Severe falciparum malaria is a major cause of death in tropical countries, particularly in African children. Rapid and accurate diagnosis and prognostic assessment are critical to clinical management. In 6027 prospectively studied patients diagnosed with severe malaria we assess the prognostic value of peripheral blood film counts of malaria pigment containing polymorphonuclear leukocytes (PMNs) and monocytes.

Towards harmonization of microscopy methods for malaria clinical research studies.

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this.

Deep Learning for Smartphone-Based Malaria Parasite Detection in Thick Blood Smears.

Objective: This work investigates the possibility of automated malaria parasite detection in thick blood smears with smartphones.

Methods: We have developed the first deep learning method that can detect malaria parasites in thick blood smear images and can run on smartphones. Our method consists of two processing steps.

Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria.

Background: Artemisinin resistance in falciparum malaria is associated with kelch13 propeller mutations, reduced ring stage parasite killing, and, consequently, slow parasite clearance. We assessed how parasite age affects parasite clearance in artemisinin resistance.

Methods: Developmental stages of Plasmodium falciparum parasites on blood films performed at hospital admission and their kelch13 genotypes were assessed for 816 patients enrolled in a multinational clinical trial of artemisinin combination therapy.

Understanding the learned behavior of customized convolutional neural networks toward malaria parasite detection in thin blood smear images.

Convolutional neural networks (CNNs) have become the architecture of choice for visual recognition tasks. However, these models are perceived as black boxes since there is a lack of understanding of the learned behavior from the underlying task of interest. This lack of transparency is a serious drawback, particularly in applications involving medical screening and diagnosis since poorly understood model behavior could adversely impact subsequent clinical decision-making.

Pre-trained convolutional neural networks as feature extractors toward improved malaria parasite detection in thin blood smear images.

Malaria is a blood disease caused by the parasites transmitted through the bite of female Anopheles mosquito. Microscopists commonly examine thick and thin blood smears to diagnose disease and compute parasitemia. However, their accuracy depends on smear quality and expertise in classifying and counting parasitized and uninfected cells.

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial.

Background: Acute kidney injury independently predicts mortality in falciparum malaria. It is unknown whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria.

Methods: This phase 2, open-label, randomized controlled trial conducted at two hospitals in Bangladesh assessed effects on renal function, safety, pharmacokinetic (PK) properties and pharmacodynamic (PD) effects of acetaminophen.

Image analysis and machine learning for detecting malaria.

Malaria remains a major burden on global health, with roughly 200 million cases worldwide and more than 400,000 deaths per year. Besides biomedical research and political efforts, modern information technology is playing a key role in many attempts at fighting the disease. One of the barriers toward a successful mortality reduction has been inadequate malaria diagnosis in particular.

Disease Severity and Effective Parasite Multiplication Rate in Falciparum Malaria.

Patients presenting with severe falciparum malaria in a Bangladeshi tertiary hospital had higher total parasite burden, estimated by parasitemia and plasma PfHRP2, than uncomplicated malaria patients despite shorter fever duration. This suggests that higher parasite multiplication rates (PMR) contribute to causing the higher biomass found in severe disease. Compared with patients without a history of previous malaria, patients with previous malaria carried a lower parasite biomass with similar fever duration at presentation, suggesting that host immunity reduces the PMR.

Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria.

Severe Malaria: Even with the best available treatment, the mortality from severe Plasmodium falciparum malaria remains high. Typical features at death are high parasite loads and obstructed micro- vasculature. Infected erythrocytes (IE) containing mature parasites bind to the host receptor heparan sulfate, which is also an important receptor for merozoite invasion.

Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study.

Background: Intravascular hemolysis is an intrinsic feature of severe malaria pathophysiology but the pathogenic role of cell-free hemoglobin-mediated oxidative stress in severe malaria associated acute kidney injury (AKI) is unknown.

Methods: As part of a prospective observational study, enrolment plasma cell-free hemoglobin (CFH), lipid peroxidation markers (F-isoprostanes (F-IsoPs) and isofurans (IsoFs)), red cell deformability, and serum creatinine were quantified in Bangladeshi patients with severe falciparum malaria (n = 107), uncomplicated malaria (n = 80) and sepsis (n = 28). The relationships between these indices and kidney function and clinical outcomes were examined.

Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria.

Background: Fever is an inherent symptom of malaria in both adults and children. Paracetamol (acetaminophen) is the recommended antipyretic as it is inexpensive, widely available and has a good safety profile, but patients may not be able to take the oral drug reliably. A comparison between the pharmacokinetics of oral syrup and intramuscular paracetamol given to patients with acute falciparum malaria and high body temperature was performed.

The role of previously unmeasured organic acids in the pathogenesis of severe malaria.

Introduction: Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria.

Methods: In this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh.

Defining the in vivo phenotype of artemisinin-resistant falciparum malaria: a modelling approach.

Background: Artemisinin-resistant falciparum malaria has emerged in Southeast Asia, posing a major threat to malaria control. It is characterised by delayed asexual-stage parasite clearance, which is the reference comparator for the molecular marker 'Kelch 13' and in vitro sensitivity tests. However, current cut-off values denoting slow clearance based on the proportion of individuals remaining parasitaemic on the third day of treatment ('day-3'), or on peripheral blood parasite half-life, are not well supported.

Spread of artemisinin resistance in Plasmodium falciparum malaria.

Background: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies.

Methods: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa).

Magnetic resonance imaging of the brain in adults with severe falciparum malaria.

Background: Magnetic resonance imaging (MRI) allows detailed study of structural and functional changes in the brain in patients with cerebral malaria.

Methods: In a prospective observational study in adult Bangladeshi patients with severe falciparum malaria, MRI findings in the brain were correlated with clinical and laboratory parameters, retinal photography and optic nerve sheath diameter (ONSD) ultrasound (a marker of intracranial pressure).

Results: Of 43 enrolled patients, 31 (72%) had coma and 12 (28%) died.

Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia.

Background: Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine.

Methods: Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate.

Prognostic indicators in adults hospitalized with falciparum malaria in Western Thailand.

Background: Severe malaria remains a major cause of death and morbidity amongst adults in the Asiatic tropics.

Methods: A retrospective analysis of the clinical and laboratory data of 988 adult patients, hospitalized with Plasmodium falciparum malaria and prospectively recruited to malaria studies in western Thailand between 1986 and 2002, was performed to assess the factors associated with a fatal outcome. Different severity scores and classifications for defining severe malaria were compared and, using multiple logistic regression, simple models for predicting mortality developed.

An automatic vision-based malaria diagnosis system.

Malaria is a worldwide health problem with 225 million infections each year. A fast and easy-to-use method, with high performance is required to differentiate malaria from non-malarial fevers. Manual examination of blood smears is currently the gold standard, but it is time-consuming, labour-intensive, requires skilled microscopists and the sensitivity of the method depends heavily on the skills of the microscopist.

Effect of high-dose or split-dose artesunate on parasite clearance in artemisinin-resistant falciparum malaria.

Background: The emergence of Plasmodium falciparum resistance to artemisinins on the Cambodian and Myanmar-Thai borders poses severe threats to malaria control. We investigated whether increasing or splitting the dose of the short-half-life drug artesunate improves parasite clearance in falciparum malaria in the 2 regions.

Methods: In Pailin, western Cambodia (from 2008 to 2010), and Wang Pha, northwestern Thailand (2009-2010), patients with uncomplicated falciparum malaria were randomized to oral artesunate 6 mg/kg/d as a once-daily or twice-daily dose for 7 days, or artesunate 8 mg/kg/d as a once-daily or twice-daily dose for 3 days, followed by mefloquine.

Defining falciparum-malaria-attributable severe febrile illness in moderate-to-high transmission settings on the basis of plasma PfHRP2 concentration.

Background: In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects the total body parasite burden. We aimed to define the malaria-attributable fraction of severe febrile illness, using the distributions of plasma P.

Effects of antimalarial drugs on movement of Plasmodium falciparum.

In vitro antimalarial drug susceptibility is conventionally assessed by the concentration dependent growth inhibition of Plasmodium in an in vitro culture system. Inhibition of the kinetic properties of the parasites could provide an alternative method to assess in vitro antimalarial drugs sensitivity. In this study we used a novel real time microscopic technique, which does not require fixation and staining of the parasite, to study the effects of antimalarial drugs on the intracellular movement of Plasmodium (P.

Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement.

Background: In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden.

Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria.

Background: Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements.