A Simplified, Low-Cost Method for Polarized Light Microscopy

Malaria pigment is an intracellular inclusion body that appears in blood and tissue specimens on microscopic examination and can help in establishing the diagnosis of malaria. In simple light microscopy, it can be difficult to discern from cellular background and artifacts. It has long been known that if polarized light microscopy is used, malaria pigment can be much easier to distinguish. However, this technique is rarely used because of the need for a relatively costly polarization microscope. We describe a simple and economical technique to convert any standard light microscope suitable for examination of malaria films into a polarization microscope

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

Artemisinin Antimalarials: Preserving the “Magic Bullet”

The artemisinins are the most effective antimalarial drugs known. They possess a remarkably wide therapeutic index. These agents have been used in traditional Chinese herbal medicine for more than 2,000 years but were not subjected to scientific scrutiny until the 1970s. The first formal clinical trials of the artemisinins, and the development of methods for their industrial scale production, followed rapidly. A decade later, Chinese scientists shared their findings with the rest of the world; since then, a significant body of international trial evidence has confirmed these drugs to be far superior to any available alternatives. In particular, they have the ability to rapidly kill a broad range of asexual parasite stages at safe concentrations that are consistently achievable via standard dosing regimens. As their half-life is very short, there was also thought to be a low risk of resistance. These discoveries coincided with the appearance and spread of resistance to all the other major classes of antimalarials. As a result, the artemisinins now form an essential element of recommended first-line antimalarial treatment regimens worldwide. To minimize the risk of artemisinin resistance, they are recommended to be used to treat uncomplicated malaria in combination with other antimalarials as artemisinin combination therapies (ACTs). Their rollout has resulted in documented reductions in malaria prevalence in a number of African and Asian countries. Unfortunately, there are already worrisome early signs of artemisinin resistance appearing in western Cambodia. If this resistance were to spread, it would be disastrous for malaria control efforts worldwide. The enormous challenge for the international community is how to avert this catastrophe and preserve the effectiveness of this antimalarial “magic bullet”. Drug Dev Res 71: 12–19, 2010. © 2009 Wiley-Liss, Inc

Preliminary estimation of temporal and spatiotemporal dynamic measures of COVID-19 transmission in Thailand

Background As a new emerging infectious disease pandemic, there is an urgent need to understand the dynamics of COVID-19 in each country to inform planning of emergency measures to contain its spread. It is essential that appropriate disease control activities are planned and implemented in a timely manner. Thailand was one of the first countries outside China to be affected with subsequent importation and domestic spread in most provinces in the country. Method A key ingredient to guide planning and implementation of public health measures is a metric of transmissibility which represents the infectiousness of a disease. Ongoing policies can utilize this information to plan appropriately with updated estimates of disease transmissibility. Therefore we present descriptive analyses and preliminary statistical estimation of reproduction numbers over time and space to facilitate disease control activities in Thailand. ResultsThe estimated basic reproduction number for COVID-19 during the study ranged from 2.23–5.90, with a mean of 3.75. We also tracked disease dynamics over time using temporal and spatiotemporal reproduction numbers. The results suggest that the outbreak was under control since the middle of April. After the boxing stadium and entertainment venues, the numbers of new cases had increased and spread across the country. Discussion Although various scenarios about assumptions were explored in this study, the real situation was difficult to determine given the limited data. More thorough mathematical modelling would be helpful to improve the estimation of transmissibility metrics for emergency preparedness as more epidemiological and clinical information about this new infection becomes available. However, the results can be used to guide interventions directly and to help parameterize models to predict the impact of these interventions

Risks and challenges in COVID-19 infection prevention and control in a hospital setting: Perspectives of healthcare workers in Thailand

Introduction: In hospital settings, awareness of, and responsiveness to, COVID-19 are crucial to reducing the risk of transmission among healthcare workers and protecting them from infection. Healthcare professionals can offer insights into the practicalities of infection prevention and control (IPC) measures and on how the guideline aimed to ensure adherence to IPC, including use of personal protective equipment (PPE), could best be delivered during the pandemic. To inform future development of such guideline, this study examined the perspectives of healthcare professionals working in a large hospital during the pandemic regarding their infection risks, the barriers or facilitators to implementing their tasks and the IPC measures to protect their safety and health and of their patients. Method: In-depth interviews were conducted with 23 hospital staff coming into contact with possible or confirmed cases of COVID-19, or were at potential risk of contracting the disease, including medical doctors, nurses, virology laboratory staff, and non-medical workers. This qualitative study was carried out as part of a knowledge, attitudes and practice survey to prevent COVID-19 transmission at Ramathibodi Hospital in Thailand. We used content analysis to categorize and code transcribed interview data. Existing IPC guideline and evidence synthesis of organisational, environmental, and individual factors to IPC adherence among healthcare workers were used to guide the development of the interview questions and analysis. Finding: Factors identified as influencing the use of, and adherence to, prevention measures among healthcare workers included knowledge, perceived risk and concerns about the infection. The extent to which these factors were influential varied based on the medical procedures, among other features, that individuals were assigned to perform in the hospital setting. Beyond availability of PPE and physical safety, ease of and readiness to utilize the equipment and implement IPC measures were crucial to motivate hospital staff to follow the practice guideline. Having a ventilated outdoor space for screening and testing, and interaction through mobile technology, facilitated the performance of healthcare workers while reducing the transmission risk for staff and patients. Adequate training, demonstration of guided practices, and streamlined communications are crucial organisational and management support factors to encourage appropriate use of, and adherence to, implementation of infection prevention and control measures among healthcare workers. Conclusion: This finding could help inform the development of recommendations to optimise compliance with appropriate use of these measures, and to improve guidance to reduce HCW’s risk of disease in hospital settings. Further study should explore the perceptions and experiences of health professionals in smaller health facilities and community-based workers during the pandemic, particularly in resource-limited settings

Infectivity of Chronic Malaria Infections and Its Consequences for Control and Elimination

Assessing the importance of targeting the chronic Plasmodium falciparum malaria reservoir is pivotal as the world moves toward malaria eradication. Through the lens of a mathematical model, we show how, for a given malaria prevalence, the relative infectivity of chronic individuals determines what intervention tools are predicted be the most effective. Crucially, in a large part of the parameter space where elimination is theoretically possible, it can be achieved solely through improved case management. However, there are a significant number of settings where malaria elimination requires not only good vector control but also a mass drug administration campaign. Quantifying the relative infectiousness of chronic malaria across a range of epidemiological settings would provide essential information for the design of effective malaria elimination strategies. Given the difficulties obtaining this information, we also provide a set of epidemiological metrics that can be used to guide policy in the absence of such data

Malarial Retinopathy in Bangladeshi Adults

To establish if assessment of malarial retinopathy in adult malaria using ophthalmoscopy by non-ophthalmologists has clinical and prognostic significance, 210 Bangladeshi adults were assessed by both direct and indirect ophthalmoscopy; 20 of 20 healthy subjects and 20 of 20 patients with vivax malaria showed no retinal changes, whereas in patients with falciparum malaria, indirect ophthalmoscopy revealed malarial retinopathy (predominantly retinal hemorrhages) in 18 of 21 (86%) fatal, 31 of 75 (41%) cerebral, 16 of 64 (25%) non-cerebral but severe, and 1 of 31 (3%) uncomplicated cases. Direct ophthalmoscopy missed retinopathy in one of these cases and found fewer retinal hemorrhages (mean difference = 3.09; 95% confidence interval = 1.50–4.68; P < 0.0001). Severity of retinopathy increased with severity of disease (P for trend < 0.0001), and renal failure, acidosis, and moderate/severe retinopathy were independent predictors of mortality by both ophthalmoscopic techniques. Direct ophthalmoscopy by non-ophthalmologists is an important clinical tool to aid diagnosis and prognosis in adults with severe malaria, and indirect ophthalmoscopy by non-ophthalmologists, although more sensitive, provides minimal additional prognostic information