Community Welfare Society Hospital

Malaria in the rural and remote regions of tropical countries remain a major public health challenge. Early diagnosis and prompt effective treatment are the basis for the management of malaria and for reducing malaria mortality and morbidity worldwide and the key to malaria elimination. While Rapid Diagnostic Test (RDT) remains the current mainstay testing malaria infections, it is usually used in conjunction with clinical findings and lab tests of blood films through Microscopy- the gold standard of malaria diagnosis. Recent reports suggest that the accuracy of RDTs could be compromised due to parasite antigen gene deletion(s), and the lack of expertise and high turnover time makes microscopy impractical to be used in rural and remote areas which impede the diagnosis and treatment of the disease. Delay in receiving treatment for uncomplicated malaria is reported to increase the risk of developing severe malaria and mortality. Thus, the need to develop advanced, faster, and smarter tools for malaria diagnosis is paramount, specially to reinforce the gold standard method, i.e., malaria microscopy which is a full-proof tool given the limitations be addressed. Deep learning-based methods have proven to provide human expert level performance on object detection/classification on image data. Such methods can be utilized for automation of repetitive task in assessing large number of microscope images of blood samples. In this paper, we propose a novel approach to improve the performance of deep learning models through consistent labelling of ground truth bounding box for the task of pathogen detection on microscope images of thick blood smears. Recommendations are made on the reliability and repeatability testing of the trained models. A custom deep learning architecture (YOLO-mp) is developed based on the design criteria of optimizing accuracy and speed of detection with minimal resources. The custom three-layered YOLO-mp-3l and four-layered YOLO-mp-4l models achieved the best mAP scores of 93.99 (@IoU=0.5) and 94.07 (@IoU=0.5), respectively outperforming standard YOLOv4 (mAP 92.56 @IoU=0.5) for detection of malaria pathogen on a public dataset of thick blood smear microscope images captured using phone camera. YOLO-mp-3l (BFLOPs =21.8, model size =24.5Mb) and YOLO-mp-4l (BFLOPs=24.477, model size =25.4Mb) outperformed standard YOLOv4 (BFLOPs=127.232, model size = 244Mb) in terms of computation and memory requirements proving them suitable to run on low resource devices.

BACKGROUND: Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicatedPlasmodium falciparummalaria. METHODS: In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42. RESULTS: Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable. CONCLUSIONS: AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance. CLINICAL TRIALS REGISTRATION: India. CTRI/2009/091/000101.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been recommended for the treatment of falciparum malaria by the World Health Organization. Though India has already switched to ACT for treating falciparum malaria, there is need to have multiple options of alternative forms of ACT. A randomized trial was conducted to assess the safety and efficacy of the fixed dose combination of artesunate-amodiaquine (ASAQ) and amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria for the first time in India. The study sites are located in malaria-endemic, chloroquine-resistant areas. METHODS: This was an open label, randomized trial conducted at two sites in India from January 2007 to January 2008. Patients between six months and 60 years of age having Plasmodium falciparum mono-infection were randomly allocated to ASAQ and AQ arms. The primary endpoint was 28-day PCR-corrected parasitological cure rate. RESULTS: Three hundred patients were enrolled at two participating centres, Ranchi, Jharkhand and Rourkela, Odisha. Two patients in AQ arm had early treatment failure while there was no early treatment failure in ASAQ arm. Late treatment failures were seen in 13 and 12 patients in ASAQ and AQ arms, respectively. The PCR-corrected cure rates in intent-to-treat population were 97.51% (94.6-99.1%) in ASAQ and 88.65% (81.3-93.9%) in AQ arms. In per-protocol population, they were 97.47% (94.2-99.2%) and 88.30% (80-94%) in ASAQ and AQ arms respectively. Seven serious adverse events (SAEs) were reported in five patients, of which two were reported as related to the treatment. All SAEs resolved without sequel. CONCLUSION: The fixed dose combination of ASAQ was found to be efficacious and safe treatment for P. falciparum malaria. Amodiaquine also showed acceptable efficacy, making it a suitable partner of artesunate. The combination could prove to be a viable option in case India opts for fixed dose combination ACT. CLINICAL TRIAL REGISTRY: ISRCTN84408319.

The Indian state of Odisha has a longstanding battle with forest malaria. Many remote and rural villages have poor access to health care, a problem that is exacerbated during the rainy season when malaria transmission is at its peak. Approximately 62% of the rural population consists of tribal groups who are among the communities most negatively impacted by malaria. To address the persistently high rates of malaria in these remote regions, the Odisha State Malaria Control Program introduced 'malaria camps' in 2017 where teams of health workers visit villages to educate the population, enhance vector control methods, and perform village-wide screening and treatment. Malaria rates declined statewide, particularly in forested areas, following the introduction of the malaria camps, but the impact of the intervention is yet to be externally evaluated. This study protocol describes a cluster-assigned quasi-experimental stepped-wedge study with a pretest-posttest control group design that evaluates if malaria camps reduce the prevalence of malaria, compared to control villages which receive the usual malaria control interventions (e.g. IRS, ITNs), as detected by PCR.

The present study is done to study different aspects of Helicobacter pylori (H. pylori) such as its prevalence, association with upper gastrointestinal pathology, diagnosis and treatment outcome. Gastric antral biopsy and serology for H. pylori was done for all dyspeptic patients. Histopathology, gram stain and biopsy urease test was done from the gastric biopsy specimen. The prevalence of H. pylori infection was 58.8%. The sensitivity, specificity, positive and negative predictive value for histopathology was 96.9%, 100%, 100% and 95.8%, respectively; for biopsy urease test 80.4%, 100%, 100% and 78.2%, respectively; for gram stain 85.6%, 97.1%, 97.6% and 82.5%, respectively, and for serology 94.8%, 77.9%, 86% and 91.4%, respectively. Mostly peptic ulcer and duodenitis cases followed by chronic active gastritis were associated with H. pylori infection. Repeat biopsy revealed eradication of H. pylori in 90.7% cases. In dyspeptic patients, endoscopic biopsy not only detects H. pylori infection, but also reveals different gastric pathologies.

Cerebral malaria is an important cause of mortality and neurodisability in endemic regions. We show magnetic resonance imaging (MRI) features suggestive of cytotoxic and vasogenic cerebral edema followed by microhemorrhages in 2 adult UK cases, comparing them with an Indian cohort. Long-term follow-up images correlate ongoing changes with residual functional impairment.

Introduction The scope of anesthesia has shifted from general anesthesia (GA) and spinal anesthesia (SA) for below-knee surgery to peripheral nerve blocks (PNB). Combined sciatic-femoral nerve block (SFNB) with ultrasound (USG) guidance can be a better format for use. Objectives The primary objectives were to compare the duration of onset of sensory and motor blockade, total duration of sensory and motor blockade, and time of first analgesic requirement between both groups. Methods A prospective, randomized comparative study was carried out at a tertiary care teaching hospital in Odisha, India, from April 2019 to April 2021 in the Department of Anaesthesiology. Patients admitted for elective below-knee surgeries with American Society of Anesthesiology (ASA) grade II or less were divided into two groups (Group A receiving USG-guided SFNB and group B receiving SA) by computer-generated sampling. The block randomization method was used to ensure equal samples in both groups. Data collection was done using the Magpi software (Magpi, Inc., Washington, D.C., United States) on android-based mobile phones. Data were analyzed using Stata Statistical Software: Release 12 (2011; StrataCorp LP, College Station, Texas, United States) for analysis. Relevant statistical tests were used to compare the results between the groups (independent sample t-test or Wilcoxson signed-rank test). Repeated measures ANOVA (RM-ANOVA) was used to check the hemodynamic stability within the groups. Results Thirty-seven subjects were enrolled in each arm (Group A and Group B). Baseline parameters in both groups were comparable. The most common indication among the study subjects was single or multiple meta-tarsal fractures (20, 27.0%) followed by malleolus (15, 20.3%) and calcaneum fractures (13, 17.6%). Most of the study subjects were from ASA grade I (around 80%). The time of onset of sensory and motor block was found to be more for USG-guided SFNB (8.08±2.11 minutes and 11.35±1.84 minutes, respectively) as compared to the SA group (3.03±0.50 minutes and 4.89±0.52 minutes, respectively) (p<0.001). Total anesthesia and time to first analgesic requirement were, however, more in USG-guided SFNB (349.43±53.49 minutes and 339.73±54.24 minutes, respectively) as compared to the SA group (137.30±34.21 minutes and 137.30±34.21 minutes, respectively) (p<0.001). The mean time to first urination in USG-guided SFNB (178.92±20.92) was significantly less (p<0.001) compared to the SA group (419.19±40.30). There were no adverse events (0%) in USG-guided SFNB while 64.9% of the subjects in the SA group experienced adverse events (p<0.001). The most common adverse events were nausea/vomiting and hypotension (around 50% for both). Hemodynamic stability was present in both the groups of anesthesia subjects, though fluctuations in blood pressure may be seen more frequently in cases of SA. All the subjects in both the groups had achieved a Bromage score of 3 universally. The grand mean score of pain by SA (2.347±0.044) was more (p<0.001) in comparison to that in subjects with USG-guided SFNB (1.961±0.073) and this was significant in both the groups. The mean increase in pain score at 24 hours in comparison to baseline was, however, significantly more (p<0.05) in the SA group (1.784±0.111) in comparison to those receiving USG-guided SFNB (1.324±0.190). Conclusion USG-guided SFNB is a better option for below-knee surgeries as compared to SA.

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, variations in brain swelling with regard to the age of patients, parasite biomass, and parasite-typing, the essential pathogenetic mechanisms underlying clinical CM have remained elusive. However, a recent series of studies based on molecular, immunologic, and advanced neuroradiologic and machine-learning approaches have unraveled new trends and insights to better understand and focus on the key determinants of CM in humans. This could possibly be the beginning of the design of new and effective adjunctive therapies that may not be common or applicable to the entire malarious world, but that could, rather, be specific to the variations in the determinants of CM.

The Center for the Study of Complex Malaria in India (CSCMi) is one of 10 International Centers of Excellence in Malaria Research funded by the National Institutes of Health since 2010. The Center combines innovative research with capacity building and technology transfer to undertake studies with clinical and translational impact that will move malaria control in India toward the ultimate goal of malaria elimination/eradication. A key element of each research site in the four states of India (Tamil Nadu, Gujarat, Odisha, and Meghalaya) has been undertaking community- and clinic-based epidemiology projects to characterize the burden of malaria in the region. Demographic and clinical data and samples collected during these studies have been used in downstream projects on, for example, the widespread use of mosquito repellants, the population genomics of Plasmodium vivax, and the serological responses to P. vivax and Plasmodium falciparum antigens that reflect past or present exposure. A focus has been studying the pathogenesis of severe malaria caused by P. falciparum through magnetic resonance imaging of cerebral malaria patients. Here we provide a snapshot of some of the basic and applied research the CSCMi has undertaken over the past 12 years and indicate the further research and/or clinical and translational impact these studies have had.

The identification of malaria infection using microscope images of blood smears is considered as a 'gold standard'. The diagnosis of malaria needs expert microscopists which are scarce in remote areas where malaria is endemic. Therefore, it is desirable to automate the repetitive task of pathogen detection in the blood samples received as microscope images. This study provides an easy to use and deploy method for implementing a malaria pathogen detection software- the Intelligent Suite. The Intelligent Suite features a graphical user interface (GUI) implemented using 'cvui' library to interact with the OpenVINO's inference engine for model optimisation and deployment across several inference devices. The intelligent Suite uses a custom YOLO-mp-3l model trained on Darknet framework for detection of malaria pathogen in thick smear microscope images. Moreover, the Intelligent Suite provides user interface for inference device/mode selection, alter model parameters, and generate detection reports along with the model performance metrics. The Intelligent Suite was executed on a CPU computer with model inference running on a plug-and-play Neural Compute Stick (NCS2) and performance reported.

The application of neuroimaging techniques to patients with Plasmodium falciparum infection has uncovered a wide range of brain changes not only in cerebral malaria but also in noncomatose patients. We propose several hypotheses to unify findings across the spectrum of clinical malaria in adults and highlight the urgent need to evaluate potential long-term effects of cerebral alterations on neurocognition in this understudied age group.

Durgama Anchalare Malaria Nirakaran (DAMaN) is a multi-component malaria intervention for hard-to-reach villages in Odisha, India. The main component, malaria camps (MCs), consists of mass screening, treatment, education, and intensified vector control. We evaluated MC effectiveness using a quasi-experimental cluster-assigned stepped-wedge study with a pretest-posttest control group in 15 villages: six immediate (Arm A), six delayed (Arm B), and three previous interventions (Arm C). The primary outcome was PCR + Plasmodium infection prevalence. The time (i.e., baseline vs. follow-up 3) x study arm interaction term shows that there were statistically significant lower odds of PCR + Plasmodium infection in Arm A (AOR = 0.36, 95% CI = 0.17, 0.74) but not Arm C as compared to Arm B at the third follow-up. The cost per person ranged between US$3-8, the cost per tested US$4-9, and the cost per treated US$82-1,614, per camp round. These results suggest that the DAMaN intervention is a promising and financially feasible approach for malaria control.

The Center for the Study of Complex Malaria in India (CSCMi) was launched in 2010 with the overall goal of addressing major gaps in our understanding of "complex malaria" in India through projects on the epidemiology, transmission, and pathogenesis of the disease. The Center was mandated to adopt an integrated approach to malaria research, including building capacity, developing infrastructure, and nurturing future malaria leaders while conducting relevant and impactful studies to assist India as it moves from control to elimination. Here, we will outline some of the interactions and impacts the Center has had with malaria policy and control counterparts in India, as well as describe emerging needs and new research questions that have become apparent over the past 12 years.

Digestion of food forms an essential process in a living organism. Digestion of food can be classified into two categories: (1) mechanical digestion and (2) chemical digestion. Whereas mechanical digestion contributes to the physical breakdown of food using mechanical forces, chemical digestion contributes via breaking down the chemical bonds present in the food. The process is manifested by muscular contraction. The intestine develops undulations via contraction of the muscle fiber that involves contraction and relaxation of muscle fibers (referred to as the peristalsis). As a consequence, the momentum generated by the muscular contraction serves to develop fluid motion in the lumen, which eventually leads to mixing and transport. Whereas the bodily secretions of the digestive enzymes participate in innate digestion, the gut flora, on the other hand, also influence digestion to an extent by means of fermentation. Small intestinal peristalsis serves as the key mediator, whether the digestion proceeds normally during physiology or abnormally leading to pathology.

Objective: To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain (Pf3D7), its clinical isolate (Pf140/SS), and Plasmodium berghei ANKA (PbA). Methods: Using ring-stage survival assay, phenotypic assessments, and SYBR-green-based fluorescence assay, the antimalarial activities of noscapine were assessed compared with dihydroartemisinin (DHA) in in vivo and in vitro studies. In addition, hemolysis and cytotoxicity tests were carried out to evaluate its safety. RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2 (PfFP-2). Results: The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA, with IC 50 values of (7.68±0.88) and (5.57±0.74) nM/mL, respectively, and &gt;95% inhibition of PbA infected rats. Noscapine also showed a safe profile, as evidenced by low hemolysis and cytotoxicity even at high concentrations. Moreover, PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS ( P &lt;0.01). Conclusions: Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles, which may be further explored as a therapeutic candidate for the treatment of malaria.

Diagnostic escape via Plasmodium falciparum (P. falciparum) histidine-rich protein 2 (pfhrp2) gene deletions is a major potential hurdle for global malaria elimination efforts. We investigated the prevalence of pfhrp2 gene deletions in 15 malaria-endemic villages in the state of Odisha, India, and modeled their impact on an ongoing in-country malaria intervention program. We found that 61.6% of subpatent P. falciparum infections (i.e., rapid diagnostic test [RDT]-negative and positive by polymerase chain reaction [PCR]) had pfhrp2 gene deletions, which were predominantly located in the exon 2 region (96.2%) and largely identified in samples from febrile individuals (82.6%). DNA sequencing and protein diversity features were characterized in a subset of samples from individuals with subpatent infections carrying intact pfhrp2 exon 2 loci. Our analyses revealed novel amino acid repeat motifs (231-293 amino acids), and these variant repeat sequences differed from those of RDT+/PCR+ samples. We also evaluated the state-sponsored mass screening and treatment intervention in the context of pfhrp2 gene deletions. We found that mass screening and treatment conducted alongside additional interventions (e.g., long-lasting insecticidal net distribution, indoor residual spraying) reduced the relative risk of infection for both P. falciparum parasites harboring a pfhrp2 deletion (adjusted relative risk ratio [aRRR] = 0.3; 95% CI = 0.1-1.0) and P. falciparum parasites with intact pfhrp2 genes (aRRR = 0.4; 95% CI = 0.2-1.1) when compared with the use of mass screening and treatment by RDT alone. Combined, our findings highlight the need for alternative diagnostic targets and tools as India moves toward its goal of malaria elimination by 2030.

Abstract Malaria is a global public health menace. The quest for new antimalarials and adjuvants for malaria in the backdrop of artemisinin resistance has been enormous. This study evaluates the comprehensive antimalarial activity of the natural phytochemical compound Noscapine, against Plasmodium falciparum 3D7 strain (Pf3D7), clinical isolate (Pf140/SS) and in Plasmodium berghei ANKA (PbA), inhibiting in vitro and in vivo parasite growth under controlled conditions as evaluated through the ring-stage survival assay, phenotypic assessments and SYBR-green based fluorescence assay. Cytotoxicity of Noscapine was evaluated against the J774. A.1 murine macrophage cell line besides profiling its hemolysis activities against human RBCs. The antimalarial efficacy of Noscapine against Pf3D7 and Pf140/SS was similar or better than standard antimalarial Dihydroartemisinin (DHA), with the IC50 value of 7.68±0.88 and 5.57±0.74 nM/mL respectively along with more than 95% inhibition in infected Wister albino rats with PbA after 4-day suppressive test. Importantly, unlike DHA, no toxicity symptoms were observed with CC 50 value 1748 nM/mL or hemolysis with Nospcapine, even at extremely high concentrations. Based on the published literature as on date, this is the first report on native Noscapine, which has shown potent antimalarial efficacy and safety profiles vis-à-vis standard antimalarial DHA, demonstrated through in vitro and in vivo models of animal and clinical malaria parasites .

Durgama Anchalare Malaria Nirakaran (DAMaN) is a multi-component malaria intervention for hard-to-reach villages in Odisha, India. The main component, Malaria Camps (MCs), consists of mass screening, treatment, education, and intensified vector control. We evaluated MC effectiveness using a quasi-experimental cluster-assigned stepped-wedge study with a pretest-posttest control group in 15 villages: six immediate (Arm A), six delayed (Arm B), and three previous interventions (Arm C). The primary outcome was PCR+ Plasmodium infection prevalence. Across all arms, the odds of PCR+ malaria were 54% lower at the third follow-up compared to baseline. A time (i.e., visit) x study arm interaction revealed significantly lower odds of PCR+ malaria in Arm A versus B at the third follow-up. The cost per person ranged between US$3-8, the cost per tested US$4-7, and the cost per treated US$82-1,614, per camp round. These results suggest that the DAMaN intervention is a promising, financially feasible approach for malaria control.