Research Interests: Magnetic Resonance Imaging, Medical Microbiology, Malaria, Developing Countries, Malawi, and 15 moreComa, Humans, Child, Asia, Endemic Diseases, Brain Ischemia, Autopsy, Adult, Intensive Care Medicine, Disease Progression, Cerebral Malaria, Erythrocytes, Brain Edema, Cause of death, and Malaria Falciparum
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Research Interests: Malaria, Medicine, Humans, Pubmed, Male, and 6 moreAdult, Plasmodium falciparum, Antimalarials, Leg, Gangrene, and Malaria Falciparum
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The diagnosis of malaria poses great difficulty at times due to non-availability of microscope, trained personnel or laboratory set up. We undertook the immunochromatographic test in 98 suspected cases of malaria for the detection of... more
The diagnosis of malaria poses great difficulty at times due to non-availability of microscope, trained personnel or laboratory set up. We undertook the immunochromatographic test in 98 suspected cases of malaria for the detection of antigen of P. falciparum in the blood and to assess its sensitivity and positive predictive value. The sensitivity was 87.06% (confidence interval 77.57 to 92.55%) and the positive predictive value was 93.67%. This is a simple, sensitive and convenient test which can be performed in remote areas.
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Acute renal failure is a significant complication of falciparum malaria and is associated with increased morbidity and mortality. It occurs rarely in children and is seen frequently among the adults. Malaria associated renal failure may... more
Acute renal failure is a significant complication of falciparum malaria and is associated with increased morbidity and mortality. It occurs rarely in children and is seen frequently among the adults. Malaria associated renal failure may occur as a sole complication or as a component of multiple complications. Some of the patients may have normal urination (non-oliguric) and usually have better prognosis even without renal replacement therapy. Only a few research studies are available from Indian subcontinent on malarial acute renal failure. The present study is a hospital based study from eastern India. Rourkela is situated in the western part of Orissa which contributes a large number of falciparum malaria cases. The study was conducted at the internal medicine department of Ispat General Hospital. The clinical presentation of malaria patients in 2001 were analysed with special emphasis on malarial acute renal failure. The difference between patients with or without renal failure was compared. Seven hundred eighteen patients admitted to Ispat General Hospital in 2001 above the age of 14 years were analysed. Of these, 84 (11.8%) had serum creatinine >3 mg/dl. Seventy-five patients were referred from different hospitals outside the township. The presenting complaints were fever (95%), oliguria (55%); loose motions (25%), and vomiting (51%). Headache was present in only 20% patients. Similarly, hypotension was encountered in about a third. Associated complications were significantly more common among patients having renal failure viz, Jaundice (77 versus 19%; p < 0.001), Cerebral malaria (59 versus 11%; p < 0.001), and hypoglycaemia (p < 0.05). The mortality in presence of acute renal failure was high (p < 0.001). Though malaria renal failure is a burning issue, still scant data is available in the literature, including India. The present study is an attempt to study the patients admitted to a referral hospital. The reason for high mortality is due to presence of multiple complications. The present study indicates that the presence of acute renal failure and jaundice together adversely influences the mortality. Hence, studies may be carried out to find out the reason of this changing trend as well as the methods to ameliorate/manage the situation.
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Cytoadherence of Plasmodium falciparum-infected red blood cells (RBCs) in host microvasculature and complex regulation of the immune response are important contributors to the clinical outcome of disease. We tested the association of 23... more
Cytoadherence of Plasmodium falciparum-infected red blood cells (RBCs) in host microvasculature and complex regulation of the immune response are important contributors to the clinical outcome of disease. We tested the association of 23 single nucleotide polymorphisms (SNPs) and a microsatellite repeat in adhesion molecule genes THBS1 and ESEL, and immune regulatory molecule genes NOSII, CRP, and MBL2 with falciparum malaria in populations residing in a malaria-endemic and a non-endemic region of India. The THBS1 haplotype CCCCA (rs1478604, rs7170682, rs2664141, rs12912082, rs3743125) was a risk factor in the endemic region (relative risk = 3.78) and an ESEL SNP (rs5368, His468Tyr) associated with cerebral malaria (CM) [CM vs. non-cerebral malaria (NCM), odds ratio (OR) = 2.23, p = 0.03]. In the non-endemic region, an ESEL 3&amp;amp;amp;amp;amp;amp;#39;UTR SNP (rs5359) associated with enhanced risk of disease (OR = 3.62, p = 1 × 10(-4)) and the CT genotype of the CRP promoter SNP (C/T/A) strongly associated with protection (severe vs. control, OR = 0.29, p = 6 × 10(-5)). Long repeat alleles of the NOSII promoter microsatellite (CCTTT)n exhibited strong association with protection and the NOSII ATG haplotype (rs3729508, rs2297520, rs9282801) was strongly protective against severe malaria in both regions (endemic, severe vs. control, OR = 0.05, p = 0.0001; non-endemic, severe vs. control, OR = 0.3, p = 1 × 10(-5)). Our results suggest differential contribution of variants of the investigated genes in determining the outcome of malaria in Indian populations.
Research Interests: Immunology, Biology, Malaria, Medicine, India, and 15 moreBiological Sciences, Humans, Haplotypes, C reactive protein, Odds ratio, Plasmodium falciparum, Asian Continental Ancestry Group, Protozoan Proteins, Cerebral Malaria, Haplotype, Gene frequency, Malaria Falciparum, Medical and Health Sciences, Nitric oxide synthase type II, and Genetic predisposition to disease
... Sarah Kollie Coordinator Reproductive Health Group Gue ckedou, Guinea Franz von Roenne & David Blankhart Projet Sante rurale, GTZ Faranah, Guinea (e-mail: dmblankhart@mirinet. net.gn) 1. Antequera MG, Sua rez-Varela MM. Lessons... more
... Sarah Kollie Coordinator Reproductive Health Group Gue ckedou, Guinea Franz von Roenne & David Blankhart Projet Sante rurale, GTZ Faranah, Guinea (e-mail: dmblankhart@mirinet. net.gn) 1. Antequera MG, Sua rez-Varela MM. Lessons on humanitarian assistance. ...
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Cerebral malaria is the most common cause of non-traumatic encephalopathy in the world. The mainstay of therapy is either quinine or artemisinin, both of which are effective antimalarials. The clinical picture of cerebral malaria may... more
Cerebral malaria is the most common cause of non-traumatic encephalopathy in the world. The mainstay of therapy is either quinine or artemisinin, both of which are effective antimalarials. The clinical picture of cerebral malaria may persist or even become worse in spite of the clearance of parasites from blood. The death rate is unacceptably high even with effective antimalarials in tertiary care hospitals. The mortality increases in presence of multi organ failure (renal failure, jaundice, respiratory distress, severe anaemia, lactic acidosis, etc.). The pathogenesis of cerebral malaria is multifactorial and includes clogging, sequestration, rosette formation, release of cytokines, cerebral oedema, increased intracranial hypertension, etc. Attempts are made to use adjuvant therapy which will act through alternate mechanisms and address one or more of the pathogenetic processes. In this review, we have discussed the role of corticosteroids, pentoxifylline, desferrioxamine, mannitol and newer agents in the treatment of cerebral malaria. Though the literature on adjuvant therapy in cerebral malaria is large enough, there are a number of shortcomings in the clinical trials, many being open and non randomized or of very small sample size. Further research is of utmost importance through large multicentric, double-blind controlled trials to show the efficacy of any of these drugs.
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Research Interests: Medical Microbiology, Malaria, Treatment Outcome, Bangladesh, Adolescent, and 15 moreMedicine, India, Humans, Female, Male, Intensive Care Unit, Aged, Middle Aged, Adult, World Health Organization, Fluid Therapy, Central Venous Catheter, guidelines as topic, Malaria Falciparum, and central venous pressure
Research Interests: Nursing, Bangladesh, Medicine, Critical Care Medicine, Humans, and 15 moreHemodynamics, Blood Pressure, Female, Resuscitation, Male, Anesthesia, Young Adult, Clinical Sciences, Adult, Public health systems and services research, Fluid Therapy, Pulmonary Edema, Acid-Base Equilibrium, Severity of Illness Index, and Malaria Falciparum
To document histopathologic evidence on the pathogenic mechanism of human cerebral malaria, we used light microscopy to study brain specimens from 23 patients who died of central nervous system involvement with Plasmodium falciparum.... more
To document histopathologic evidence on the pathogenic mechanism of human cerebral malaria, we used light microscopy to study brain specimens from 23 patients who died of central nervous system involvement with Plasmodium falciparum. Sequestration of parasitized red blood cells (PRBCs) leading to cerebral capillary clogging was seen. In a few specimens, vascular clogging by PRBCs was associated with margination of mononuclear cells. In others, capillaries were virtually empty and lymphocytes and monocytes were seen in apposition (marginated) to the capillary endothelial surface. The endothelial cells appeared plump, hypertrophied, and prominent. The capillary wall appeared thickened by fibrinous material. Massive intercellular brain edema along with extravasated red blood cells, mononuclear cells, and plasmatic fluid was also noticed. In addition to hypoxia induced by PRBC-mediated vascular clogging, marginating mononuclear cells may contribute to the pathogenesis of cerebral malaria. The precise role played by this phenomenon needs further evaluation.
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... as follows: New York 0630 EDT to 0830 EDT; London 1130 GMT to 1330 GMT; Singapore 1930 SGT to 2130 SGT. ... Research Letter. You have full text access to this OnlineOpen article Haemostatic abnormalities in dengue haemorrhagic fever... more
... as follows: New York 0630 EDT to 0830 EDT; London 1130 GMT to 1330 GMT; Singapore 1930 SGT to 2130 SGT. ... Research Letter. You have full text access to this OnlineOpen article Haemostatic abnormalities in dengue haemorrhagic fever in the New Delhi outbreak, India. ...
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We analysed 110 adult patients with cerebral malaria, 38 of whom had serum creatinine above 3 mg%, to study the effect of acute renal failure (ARF) on survival. Patients with cerebral malaria had an increased risk of death (39.5% versus... more
We analysed 110 adult patients with cerebral malaria, 38 of whom had serum creatinine above 3 mg%, to study the effect of acute renal failure (ARF) on survival. Patients with cerebral malaria had an increased risk of death (39.5% versus 13.9%) when also suffering from ARF. For each one log unit increase of creatinine at admission, odds of death increased by a factor of 10.8 (95% confidence interval 3.0-39.4).
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Research Interests: Immunology, Biology, Malaria, International Cooperation, Medicine, and 14 moreDisease susceptibility, Humans, Child, Disease, Adult, Plasmodium falciparum, Age Factors, Interdisciplinary Communication, Cerebral Malaria, Plasmodium Vivax, Acute Disease, Malaria Falciparum, Medical and Health Sciences, and Malaria Vivax
There are very few reports in the literature of rhabdomyolysis in falciparum malaria and they mostly consist of single case studies. A report from Sri Lanka described a single patient with myoglobinuria and skeletal muscle necrosis.... more
There are very few reports in the literature of rhabdomyolysis in falciparum malaria and they mostly consist of single case studies. A report from Sri Lanka described a single patient with myoglobinuria and skeletal muscle necrosis. Taylor and Prosser reported a single case of rhabdomyolysis with renal failure. We report on 12 patients with evidence of skeletal muscle injury in severe malaria from Rourkela, Orissa State, India.
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Research Interests: Medical Microbiology, Malaria, Acute kidney injury, Adolescent, Medicine, and 14 moreIndia, Complication, Humans, Internal Medicine, Male, Anemia, Clinical Sciences, Middle Aged, Public health systems and services research, Plasmodium falciparum, Cerebral Malaria, Hyperbilirubinemia, Acute Disease, and Malaria Falciparum
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ABSTRACTP. falciparumparasites manipulate host metabolic processes during malaria to ensure their survival and progression, causing the host and parasite metabolic pathways to become intertwined. We analyzed metabolites to evaluate their... more
ABSTRACTP. falciparumparasites manipulate host metabolic processes during malaria to ensure their survival and progression, causing the host and parasite metabolic pathways to become intertwined. We analyzed metabolites to evaluate their potential as biomarkers for cerebral malaria (CM). Our analysis of CM (with coma) and CM-like (without coma) patients identified 835 metabolites, including lipids, amino acids, xenobiotics, peptides, nucleotides, carbohydrates, cofactors, and vitamins. Principal component analysis revealed clear segregation between CM-like and CM patients. Metabolite-by-metabolite analysis identified 103 differentially abundant metabolites, 26 of which were significantly lower in CM-like patients (primarily lipids), while 71% of those higher in CM patients were amino acids and xenobiotics. The results revealed significant differences in circulating levels of long chain free fatty acids and catecholamine metabolism and identified steroid biosynthesis as the most enri...
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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... more
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.
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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... more
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+Plasmodiuminfection 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 feasibl...
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ABSTRACT. 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,... more
ABSTRACT. 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.
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ABSTRACT. 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... more
ABSTRACT. 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 presen...
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Brain swelling occurs in cerebral malaria (CM) and may either reverse or result in fatal outcome. It is currently unknown how brain swelling in CM reverses, as investigations have been hampered by inadequate animal models. In this study,... more
Brain swelling occurs in cerebral malaria (CM) and may either reverse or result in fatal outcome. It is currently unknown how brain swelling in CM reverses, as investigations have been hampered by inadequate animal models. In this study, we show that reversible brain swelling in experimental murine cerebral malaria (ECM) can be induced reliably after single vaccination with radiation-attenuated sporozoites as revealed by in vivo high-field (9.4T) magnetic resonance imaging. Our results provide evidence that parenchymal fluid increase and consecutive brain swelling results from transcellular blood-brain barrier disruption (BBBD), as revealed by electron microscopy. This mechanism enables reversal of brain swelling but does not prevent persistent focal brain damage, evidenced by microhemorrhages, in areas of most severe BBBD. In a cohort of 27 pediatric and adult CM patients (n=4 fatal, n=23 non-fatal) two out of four fatal CM patients (50%) and 8 out of 23 non-fatal CM patients (35%)...
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<b>Copyright information:</b>Taken from "Polymorphisms of -enhancer and gene for FcγRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian... more
<b>Copyright information:</b>Taken from "Polymorphisms of -enhancer and gene for FcγRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population"http://www.malariajournal.com/content/7/1/13Malaria Journal 2008;7():13-13.Published online 14 Jan 2008PMCID:PMC2245971. A, rLD plot of four SNPs (-1031, -863, -308, -238). Value in each cell is the percent D' between SNP pairs. B, Correlation of promoter haplotype (-1031C, -863A, -857C, -308G, -238G) with elevated TNF levels compared to the major haplotype TCCGG. Mean plasma TNF levels were compared using Mann-Whitney test (z = -3.73, P = 0.0002). C, Plasma TNF level in patients and controls. Pairwise comparison of means by non-parametric Mann-Whitney test: severe versus control, z = 4.41, P &lt; 0.0001; non-severe versus control, z = 0.67, P = 0.25; severe versus non-severe, z = 3.13, P = 0.0009.
Research Interests: Molecular Biology, Correlation, Haplotypes, Plasma, Region, and 5 moreLinkage, TNF, Levels, Regulatory, and Snps
Abstract. Malarial retinopathy allows detailed study of central nervous system vascular pathology in living patients with severe malaria. An adult with cerebral malaria is described who had prominent retinal whitening with corresponding... more
Abstract. Malarial retinopathy allows detailed study of central nervous system vascular pathology in living patients with severe malaria. An adult with cerebral malaria is described who had prominent retinal whitening with corresponding retinal microvascular obstruction, vessel dilatation, increased vascular tortuosity, and blood retinal barrier leakage with decreased visual acuity, all of which resolved on recovery. Additional study of these features and their potential role in elucidating the pathogenesis of cerebral malaria is warranted. The pathogenesis of coma in falciparummalaria and its rapid reversibility are potential targets for adjunctive therapies, but they are not well-understood. Microvascular obstruction is probably an important contributor. The brain microvasculature is relatively inaccessible; it can be studied in detail only at post-mortem. Similarly, microvascular obstruction in the retina is thought to be a major contributor to the unique retinopathy of severe fa...
Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India
with the severity of falciparum malaria in the ethnically diverse
ABSTRACT 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... more
ABSTRACT 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.
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brain during Plasmodium falciparum infection in humans. The current understanding of the CM pathogenesis is believed to be at its infancy, although there have been significant advances in the recent years to investigate this... more
brain during Plasmodium falciparum infection in humans. The current understanding of the CM pathogenesis is believed to be at its infancy, although there have been significant advances in the recent years to investigate this multifactorial neuropathology which is more common in African children and Indian adults. The Indian scenario reveals that complications of CM could be mostly fatal in adults with or without multiorgan failures especially grave prognosis in the former situation. We report here the deaths of two young females with CM from Ispat General Hospital, an industrial tertiary care hospital located in a malaria endemic region, Rourkela, from the eastern Indian state of Odisha. The uniqueness of citing both these fatal CM cases is to emphasize the prognostic potential of simple tools, e.g. peripheral blood smear microscopy. Meticulous record of important microscopic features in the peripheral blood can be useful in the assessment of progression and severity of the disease,...
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Background Cerebral malaria in adults is associated with brain hypoxic changes on magnetic resonance (MR) images and has a high fatality rate. Findings of neuroimaging studies suggest that brain involvement also occurs in patients with... more
Background Cerebral malaria in adults is associated with brain hypoxic changes on magnetic resonance (MR) images and has a high fatality rate. Findings of neuroimaging studies suggest that brain involvement also occurs in patients with uncomplicated malaria (UM) or severe noncerebral malaria (SNCM) without coma, but such features were never rigorously characterized. Methods Twenty patients with UM and 21 with SNCM underwent MR imaging on admission and 44–72 hours later, as well as plasma analysis. Apparent diffusion coefficient (ADC) maps were generated, with values from 5 healthy individuals serving as controls. Results Patients with SNCM had a wide spectrum of cerebral ADC values, including both decreased and increased values compared with controls. Patients with low ADC values, indicating cytotoxic edema, showed hypoxic patterns similar to cerebral malaria despite the absence of deep coma. Conversely, high ADC values, indicative of mild vasogenic edema, were observed in both pati...