New Ways to Tackle Malaria

Malaria is one of the oldest tropical diseases and still remains a focus of attention. Sub-Saharan African countries contribute 90% of the total malaria cases in the world. The World Health Organization (WHO) has advocated eliminating this disease by 2030 with the existing strategies and tools. Many initiatives are underway by several organizations, and 38 countries have achieved the elimination goal. The main backbone of the elimination process is smart surveillance followed by prompt public health responses. The control of the disease mainly relies on treatment of malaria positive cases with anti-malarials namely artemisinin-based combination therapy (ACT) for Plasmodium falciparum. In India, chloroquine is still effective against P. vivax. Use of 8-aminoquinolines primaquine and more recently tefenoquine warrants testing of G6PD deficiency status to avoid unnecessary hemolysis. Vector control operations mainly depend on the use of long-lasting insecticidal nets (LLINs) and indoor residual spray (IRS) with insecticides. The threat of resistance draws an open challenge in both treatment and vector management. New initiatives on surveillance, treatment, chemoprevention, and vector control using modern techniques of artificial intelligence, machine learning, genetic engineering, and digital approach of community engagement have great potential to accelerate the malaria elimination process

Innovations in Vector-Borne Disease Control in India

India is the second largest populous and democratic country in the world. Several geo-ecological settings are favorable for most of the vector borne diseases (VBDs) in the country. Malaria, Lymphatic Filariasis (LF), Japanese Encephalitis (JE), Dengue (DEN), Chikungunya (CHIK) and Kala-azar (KA) are major VBDs. Kyasanur Forest Disease (KFD), Plague and Chandipura virus (CHPV) infections have limited and localized foci, but needs attention. Crimean-Congo Hemorrhagic Fever (CCHF) and Zika are recent entries in India that also need to be handled on priority. National Vector Borne Disease Control Program (NVBDCP) is responsible for control and prevention of all these diseases. Malaria, LF, JE, DEN, CHIK and Zika are transmitted by different species of mosquitoes. KA and CHPV are transmitted by shadflies, while KFD, CCHF by ticks; plague by fleas. Scrub typhus (ST) responsible for acute encephalopathy syndrome (AES) is transmitted by Leptotrombidium mite species. It needs specific and strategic action plan in view of the diversified biodiversity. New innovations to strengthen the public health responses are the main intervention protocols. Already two diseases Guineaworm (Dracunculiasis) transmitted by different species of Cyclops, and polio have been successfully eradicated/eliminated from India. Such experience would be very helpful for the elimination of malaria, LF and KA, and all are on the elimination drive

New Challenges in Malaria Elimination

In recent years, efforts to eliminate malaria has gained a tremendous momentum, and many countries have achieved this goal — but it has faced many challenges. Recent COVID-19 pandemic has compounded the challenges due to cessation of many on-field operations. Accordingly, the World Health Organization (WHO) has advocated to all malaria-endemic countries to continue the malaria elimination operations following the renewed protocols. The recent reports of artemisinin resistance in Plasmodium falciparum followed by indication of chloroquine resistance in P. vivax, and reduced susceptibility of synthetic pyrethroids used in long lasting insecticide nets are some issues hindering the elimination efforts. Moreover, long distance night migration of vector mosquitoes in sub-Saharan Africa and invasion of Asian vector Anopheles stephensi in many countries including Africa and Southeast Asia have added to the problems. In addition, deletion of histidine rich protein 2 and 3 (Pfhrp2/3) genes in P. falciparum in many countries has opened new vistas to be addressed for point-of-care diagnosis of this parasite. It is needed to revisit the strategies adopted by those countries have made malaria elimination possible even in difficult situations. Strengthening surveillance and larval source management are the main strategies for successful elimination of malaria. New technologies like Aptamar, and artificial intelligence and machine learning would prove very useful in addressing many ongoing issues related to malaria elimination

A New Outlook in Lymphatic Filariasis Elimination in India

In India, human lymphatic filariasis (LF) is the most common vector-borne disease after malaria. It is a roundworm nematode parasitic helminthiases group of diseases under Filarioidea type of infection. The parasites are found in the lymphatic system, damage the system leading to deformities of body organs. Of the eight human filarial parasites, Wuchereria bancrofti, Brugia malayi and B. timori are involved with the lymphatic system. Globally W. bancrofti is the most predominant species sharing 90% of the burden. In India, W. bancrofti and B. malayi are present. The revised control strategy was aimed at a single-dose mass drug administration (MDA) and home-based morbidity management. The Elimination of LF (ELF) was initiated in 2004 in 202 districts which were expanded later in 256 districts after a pilot study in LF endemic districts initiated in 1997. The initial start of ELF campaign was with a single drug, i.e. diethylcarbamazine (DEC), but later in 2007, a combination of two drugs DEC and albendazole (ALB) were given through MDA. Now a third drug ivermectin (IVM) has been added to accelerate the elimination process by 2020 which is the global goal of elimination under Global Programme to Eliminate Lymphatic Filariasis (GPELF)

Elevated CPW-Fed Slotted Microstrip Antenna for Ultra-Wideband Application

Elevated-coplanar-waveguide- (ECPW-) fed microstrip antenna with inverted “G” slots in the back conductor is presented. It is modeled and analyzed for the application of multiple frequency bands. The changes in radiation and the transmission characteristics are investigated by the introduction of the slots in two different positions at the ground plane (back conductor). The proposed antenna without slots exhibits a stop band from 2.55 GHz to 4.25 GHz while introducing two slots on the back conductor, two adjacent poles appear at central frequencies of 3.0 GHz and 3.9 GHz, respectively, and the antenna shows the ultra-wideband (UWB) characteristics. The first pole appears at the central frequency of 3.0 GHz and covers the band width of 950 MHz, and the second pole exists at a central frequency of 3.90 GHz covering a bandwidth of 750 MHz. Experimental result shows that impedance bandwidth of 129% (S11<-10 dB) is well achieved when the antenna is excited with both slots. Compared to most of the previously reported ECPW structures, the impedance bandwidth of this antenna is increased and also the size of the antenna becomes smaller and more suitable for many wireless applications like PCS (1850–1990 MHz), WLAN (2.4–2.484 GHz), WiMAX (2.5–2.69 GHz and 5.15–5.85 GHz), and also X-band communication

Haplotype of RNASE 3 polymorphisms is associated with severe malaria in an Indian population.

Severe malaria (SM) caused by Plasmodium falciparum (Pf) infection has been associated with life-threatening anemia, metabolic acidosis, cerebral malaria and multiorgan dysfunction. It may lead to death if not treated promptly. RNASE 3 has been linked to Pf growth inhibition and its polymorphisms found associated with SM and cerebral malaria in African populations. This study aimed to assess the association of RNASE 3 polymorphisms with SM in an Indian population. RNASE 3 gene and flanking regions were amplified followed by direct DNA sequencing in 151 Indian patients who visited Wenlock District Government Hospital, Mangalore, Karnataka, India. Allele, genotype and haplotype frequencies were compared between patients with SM (n = 47) and uncomplicated malaria (UM; n = 104). Homozygous mutant genotype was only found for rs2233860 (+ 499G > C) polymorphism ( A), rs2073342 (+ 371C > G) and rs2233860 (+ 499G > C) polymorphisms was correlated significantly with SM patients (OR = 3.03; p = 0.008) after Bonferroni correction. A haplotype of RNASE 3 gene was found associated with an increased risk of SM and confirming that RNASE 3 gene plays a role in susceptibility to SM

Clinical Proteomics of the Neglected Human Malarial Parasite Plasmodium vivax

Recent reports highlight the severity and the morbidity of disease caused by the long neglected malaria parasite Plasmodium vivax. Due to inherent difficulties in the laboratory-propagation of P. vivax, the biology of this parasite has not been adequately explored. While the proteome of P. falciparum, the causative agent of cerebral malaria, has been extensively explored from several sources, there is limited information on the proteome of P. vivax. We have, for the first time, examined the proteome of P. vivax isolated directly from patients without adaptation to laboratory conditions. We have identified 153 proteins from clinical P. vivax, majority of which do not show homology to any previously known gene products. We also report 29 new proteins that were found to be expressed in P. vivax for the first time. In addition, several proteins previously implicated as anti-malarial targets, were also found in our analysis. Most importantly, we found several unique proteins expressed by P. vivax.This study is an important step in providing insight into physiology of the parasite under clinical settings

Deregulation of LIMD1-VHL-HIF-1α-VEGF pathway is associated with different stages of cervical cancer.

To understand the mechanism of cellular stress in basal-parabasal layers of normal cervical epithelium and during different stages of cervical carcinoma, we analyzed the alterations (expression/methylation/copy number variation/mutation) of HIF-1α and its associated genes LIMD1, VHL and VEGF in disease-free normal cervix (n = 9), adjacent normal cervix of tumors (n = 70), cervical intraepithelial neoplasia (CIN; n = 32), cancer of uterine cervix (CACX; n = 174) samples and two CACX cell lines. In basal-parabasal layers of normal cervical epithelium, LIMD1 showed high protein expression, while low protein expression of VHL was concordant with high expression of HIF-1α and VEGF irrespective of HPV-16 (human papillomavirus 16) infection. This was in concordance with the low promoter methylation of LIMD1 and high in VHL in the basal-parabasal layers of normal cervix. LIMD1 expression was significantly reduced while VHL expression was unchanged during different stages of cervical carcinoma. This was in concordance with their frequent methylation during different stages of this tumor. In different stages of cervical carcinoma, the expression pattern of HIF-1α and VEGF was high as seen in basal-parabasal layers and inversely correlated with the expression of LIMD1 and VHL. This was validated by demethylation experiments using 5-aza-2'-deoxycytidine in CACX cell lines. Additional deletion of LIMD1 and VHL in CIN/CACX provided an additional growth advantage during cervical carcinogenesis through reduced expression of genes and associated with poor prognosis of patients. Our data showed that overexpression of HIF-1α and its target gene VEGF in the basal-parabasal layers of normal cervix was due to frequent inactivation of VHL by its promoter methylation. This profile was maintained during different stages of cervical carcinoma with additional methylation/deletion of VHL and LIMD1.This work was supported by CSIR (Council of Scientific and Industrial Research, Government of India)-JRF/NET grant [File No.09/030(0059)/2010-EMR-I] to Mr. C.Chakraborty, grant [Sr. No. 2121130723] from UGC (University Grants Commission, Government of India) to Mr. Sudip Samadder, grant [SR/SO/HS-116/2007] from DST (Department of Science and Technology, Government of India) to Dr. C. K. Panda and grant [ No. 60(0111)/14/EMR-II of dt.03/11/2014] from CSIR (Council of Scientific and Industrial Research, Government of India) to Dr. C. K. Pand

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe