Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from Southern Asia and South-eastern Asia, 1980-2015.

BACKGROUND: In the absence of definitive diagnosis, healthcare providers are likely to prescribe empirical antibacterials to those who test negative for malaria. This problem is of critical importance in Southern Asia (SA) and South-eastern Asia (SEA) where high levels of antimicrobial consumption and high prevalence of antimicrobial resistance have been reported. To improve management and guide further diagnostic test development, better understanding is needed of the true causative agents of fever and their geographical variability. METHODS: We conducted a systematic review of published literature (1980-2015) to characterise the spectrum of pathogens causing non-malarial febrile illness in SA and SEA. We searched six databases in English and French languages: MEDLINE, EMBASE, Global Health (CABI) database, WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. RESULTS: A total of 29,558 records from 19 countries in SA and SEA were screened, of which 2410 (8.1%) met the selection criteria. Bacterial aetiologies were reported in 1235 (51.2%) articles, viral in 846 (35.1%), parasitic in 132 (5.5%), and fungal in 54 (2.2%), and 143 (6.0%) articles reported more than one pathogen group. In descending order of frequency, Salmonella Typhi, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and coagulase negative Staphylococcus were the commonly reported bacteria, while dengue virus, chikungunya virus, Japanese encephalitis virus, hepatitis B virus, and hepatitis C virus were common viral pathogens reported. Reports of rarely reported or emerging pathogens included a case report of Borrelia burgdorferi (Lyme disease) in India in 2010 and reports of Nipah virus in Singapore and India. CONCLUSIONS: This review summarises the reported non-malaria pathogens that may cause febrile illness in SA and SEA. The findings emphasise the need of standardising the reporting of aetiological studies to develop effective, evidence-based fever management and improved surveillance. Research and development of diagnostic tools would benefit from up-to-date epidemiological reporting of the regional diversities of non-malaria fever aetiologies. TRIAL REGISTRATION: PROSPERO registration, CRD42016049281

The efficacy of playing a virtual reality game in modulating pain for children with acute burn injuries: A randomized controlled trial [ISRCTN87413556]

BACKGROUND: The management of burn injuries is reported as painful, distressing and a cause of anxiety in children and their parents. Child's and parents' pain and anxiety, often contributes to extended time required for burns management procedures, in particular the process of changing dressings. The traditional method of pharmacologic analgesia is often insufficient to cover the burnt child's pain, and it can have deleterious side effects [1,2]. Intervention with Virtual Reality (VR) games is based on distraction or interruption in the way current thoughts, including pain, are processed by the brain. Research on adults supports the hypothesis that virtual reality has a positive influence on burns pain modulation. METHODS: This study investigates whether playing a virtual reality game, decreases procedural pain in children aged 5–18 years with acute burn injuries. The paper reports on the findings of a pilot study, a randomised trial, in which seven children acted as their own controls though a series of 11 trials. Outcomes were pain measured using the self-report Faces Scale and findings of interviews with parent/carer and nurses. RESULTS: The average pain scores (from the Faces Scale) for pharmacological analgesia only was, 4.1 (SD 2.9), while VR coupled with pharmacological analgesia, the average pain score was 1.3 (SD 1.8) CONCLUSION: The study provides strong evidence supporting VR based games in providing analgesia with minimal side effects and little impact on the physical hospital environment, as well as its reusability and versatility, suggesting another option in the management of children's acute pain

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). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.)

Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Background: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery

Multi-Population Black Hole Algorithm for the Problem of Data Clustering

The retrieval of important information from a dataset requires applying a special data mining technique known as data clustering (DC). DC classifies similar objects into a groups of similar characteristics. Clustering involves grouping the data around k-cluster centres that typically are selected randomly. Recently, the issues behind DC have called for a search for an alternative solution. Recently, a nature-based optimization algorithm named Black Hole Algorithm (BHA) was developed to address the several well-known optimization problems. The BHA is a metaheuristic (population-based) that mimics the event around the natural phenomena of black holes, whereby an individual star represents the potential solutions revolving around the solution space. The original BHA algorithm showed better performance compared to other algorithms when applied to a benchmark dataset, despite its poor exploration capability. Hence, this paper presents a multi-population version of BHA as a generalization of the BHA called MBHA wherein the performance of the algorithm is not dependent on the best-found solution but a set of generated best solutions. The method formulated was subjected to testing using a set of nine widespread and popular benchmark test functions. The ensuing experimental outcomes indicated the highly precise results generated by the method compared to BHA and comparable algorithms in the study, as well as excellent robustness. Furthermore, the proposed MBHA achieved a high rate of convergence on six real datasets (collected from the UCL machine learning lab), making it suitable for DC problems. Lastly, the evaluations conclusively indicated the appropriateness of the proposed algorithm to resolve DC issues

Differential systemic gene expression profile in patients with diabetic macular edema: Responders versus nonresponders to standard treatment

Introduction: Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy. The current practice of management is a" trial and error "method of using intravitreal antivascular endothelial growth factor (VEGF)′′ or steroids to treat the patient and watch the response. However, if the patient′s genetic profile helps us choose appropriate medicine, it would help customize treatment option for each patient. This forms the basis of our study. Materials and Methods: A case-control, prospective, observational series, where DME patients were treated with bevacizumab and subclassified as treatment naοve, treatment responders, and treatment nonresponders. Blood samples of 20 subjects were studied, with five patients in each of the groups (nondiabetic- group 1, treatment naοve- group 2, treatment responder- group 3, and treatment nonresponder-group 4). Whole blood RNA extraction followed by labeling, amplification and hybridization was done, and microarray data analyzed. Genes were classified based on functional category and pathways. Results: The total number of genes upregulated among all three experimental groups was 5, whereas 105 genes were downregulated. There were no common genes upregulated between the responders and nonresponders. There was only one gene upregulated between the diabetic and diabetic responders posttreatment. There were 19 genes upregulated and 8 genes downregulated in the inflammatory pathway in group 2 versus group 1. There were no downregulated genes detected in vascular angiogenesis and transcription group. There were identical numbers of genes up- and downregulated in the inflammatory pathway. Seventeen genes were upreguated and 11 genes downregulated in receptor activity, which remained the predominant group in the group classification. Discussion: In summary, this study would provide an insight into the probable signaling mechanisms for disease pathogenesis as well as progression. This type of study eventually would aid in developing or improvising existing treatment modules with a rational approach towards personalized medicine, in future addressing the differential responses to treatment

A cross-sectional assessment of diabetes self-management, education and support needs of Syrian refugee patients living with diabetes in Bekaa Valley Lebanon

Abstract Background Patients with diabetes require knowledge and skills to self-manage their disease, a challenging aspect of treatment that is difficult to address in humanitarian settings. Due to the lack of literature and experience regarding diabetes self-management, education and support (DSMES) in refugee populations, Medecins Sans Frontieres (MSF) undertook a DSMES survey in a cohort of diabetes patients seen in their primary health care program in Lebanon. Methods Structured interviews were conducted with diabetes patients in three primary care clinics between January and February 2015. Scores (0–10) were calculated to measure diabetes core knowledge in each patient (the DSMES score). Awareness of long-term complications and educational preferences were also assessed. Analyses were conducted using Stata software, version 14.1 (StataCorp). Simple and multiple linear regression models were used to determine associations between various patient factors and the DSMES Score. Results A total of 292 patients were surveyed. Of these, 92% had type 2 diabetes and most (70%) had been diagnosed prior to the Syrian conflict. The mean DSMES score was 6/10. Having secondary education, previous diabetes education, a ‘diabetes confidant’, and insulin use were each associated with a higher DSMES Score. Lower scores were significantly more likely to be seen in participants with increasing age and in patients who were diagnosed during the Syrian conflict. Long-term complications of diabetes most commonly known by patients were vision related complications (68% of patients), foot ulcers (39%), and kidney failure (38%). When asked about the previous Ramadan, 56% of patients stated that they undertook a full fast, including patients with type 1 diabetes. Individual and group lessons were preferred by more patients than written, SMS, telephone or internet-based educational delivery models. Conclusions DSMES should be patient and context appropriate. The variety and complexities of humanitarian settings provide particular challenges to its appropriate provision. Understanding patient baseline DSMES levels and needs provides a useful basis for humanitarian organizations seeking to provide diabetes care

Triage practices for emergency care delivery: a qualitative study among febrile patients and healthcare workers in a tertiary care hospital in Nepal

Abstract Background Improving screening and triage practices is essential for early severity assessments at the first point of contact and ensuring timely attention by healthcare workers (HCWs). The main objective of this study was to explore the triage process among febrile patients and HCWs in the emergency department (ED) of a tertiary care hospital in a resource-constrained setting. Methods This qualitative study was conducted from March to May 2023 at the ED of Tribhuvan University Teaching Hospital (TUTH), Nepal. The study included in-depth interviews with febrile patients (n = 15) and HCWs (n = 15). Additionally, direct observation notes (n = 20) were collected to document the triage process and patients’ experiences in the ED. Data underwent thematic analysis using the Interpretative Phenomenological Analysis (IPA) approach. Results The ED of TUTH offered comprehensive triage services with clear delineation for the severity of febrile patients in line with the World Health Organization (WHO) guidelines. Nonetheless, challenges and constraints were identified. In the ED, evenings were generally the busiest period, and the triage process was not thorough during night shifts. Perception of triage was limited among patients and variable among HCWs. Digitalizing recordings of patient information including payment was deemed necessary for effective management of patients’ waiting times at the triage station. High patient throughput added pressure on HCWs and had a potential influence on the delivery of services. Availability of medical equipment and space were also identified as challenges, with patients sometimes compelled to share beds. There were constraints related to waste disposal, hygiene, cleanliness, and the availability and maintenance of washrooms. Febrile patients experienced delays in receiving timely consultations and laboratory investigation reports, which affected their rapid diagnosis and discharge; nonetheless, patients were satisfied with the overall healthcare services received in the ED. Conclusions Improving current triage management requires resource organization, including optimizing the waiting time of patients through a digitalized system. Urgent priorities involve upgrading visitor facilities, patient consultations, laboratory investigations, hygiene, and sanitation. HCWs’ recommendations to resource the ED with more equipment, space, and beds and a dedicated triage officer to ensure 24-hour service, together with training and incentives, warrant further attention

Hepatitis E virus infection and fulminant hepatic failure during pregnancy

Background and Aim: Hepatitis E virus (HEV) infection leading to fulminant hepatic failure (FHF) and high mortality is a common feature in Indian women during the second and third trimesters of pregnancy. An altered status of hormones and immunity are observed during pregnancy but the actual cause of high mortality is still unknown. The present study was carried out to analyze CD3, CD4 and CD8 T cell counts and to assay the level of pregnancy-related hormones such as estrogen, progesterone and &#946;-HCG in order to discover the role played by these factors. Methods: One hundred patients (50 pregnant and 50 non-pregnant women) with FHF and 150 pregnant healthy females without liver disease as controls were recruited for the study. Serological tests for all viral markers using ELISA kits and detection of HEV RNA by reverse transcription-polymerase chain reaction (RT-PCR) were carried out in all cases. CD3, CD4 and CD8 T cell counts were analyzed by fluorescence activated cell sorter (FACS) while hormone assay was performed by commercially available RIA kits. Results: Serologically (38/50; 76%) as well as by RT-PCR (28/50; 56%), a significantly higher HEV positivity rate was found in pregnant FHF patients compared to non-pregnant women (serologically 15/50; 30%; RT-PCR 7/50; 14%). CD4 counts were lower (P &lt; 0.05), while CD8 counts were higher (P &lt; 0.05), and their ratio (CD4/CD8) in HEV positive pregnant FHF patients was significantly lower (P &lt; 0.01) when compared to that of HEV negative pregnant FHF women or controls. Levels of estrogen, progesterone and &#946;-HCG were also found to be higher (P &lt; 0.001) in HEV positive pregnant FHF patients when compared to HEV negative patients or controls. HEV infected pregnant FHF patients had a significantly higher mortality rate of 65.8% (25/38) compared to 23.5% (4/15) in HEV positive non-pregnant women (P &lt; 0.001). Conclusions: Pregnancy appears to be a potential risk factor for viral replication and an extreme low immune status of Indian/Asian pregnant women. It is suggested that diminished cellular immunity (indicated by a decrease in CD4, an increase in CD8 cell counts and lowered CD4/CD8 cell ratio) and a high level of steroid hormones that influence viral replication/expression during pregnancy appear to be the plausible reasons for severity of the disease